Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • Articles  (19)
  • Female  (17)
  • *Phenotype  (3)
  • Nature Publishing Group (NPG)  (19)
  • American Chemical Society
  • Macmillian Magazines Ltd.
Collection
  • Articles  (19)
Publisher
Years
  • 1
    Publication Date: 2015-09-10
    Description: Somaclonal variation arises in plants and animals when differentiated somatic cells are induced into a pluripotent state, but the resulting clones differ from each other and from their parents. In agriculture, somaclonal variation has hindered the micropropagation of elite hybrids and genetically modified crops, but the mechanism responsible remains unknown. The oil palm fruit 'mantled' abnormality is a somaclonal variant arising from tissue culture that drastically reduces yield, and has largely halted efforts to clone elite hybrids for oil production. Widely regarded as an epigenetic phenomenon, 'mantling' has defied explanation, but here we identify the MANTLED locus using epigenome-wide association studies of the African oil palm Elaeis guineensis. DNA hypomethylation of a LINE retrotransposon related to rice Karma, in the intron of the homeotic gene DEFICIENS, is common to all mantled clones and is associated with alternative splicing and premature termination. Dense methylation near the Karma splice site (termed the Good Karma epiallele) predicts normal fruit set, whereas hypomethylation (the Bad Karma epiallele) predicts homeotic transformation, parthenocarpy and marked loss of yield. Loss of Karma methylation and of small RNA in tissue culture contributes to the origin of mantled, while restoration in spontaneous revertants accounts for non-Mendelian inheritance. The ability to predict and cull mantling at the plantlet stage will facilitate the introduction of higher performing clones and optimize environmentally sensitive land resources.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ong-Abdullah, Meilina -- Ordway, Jared M -- Jiang, Nan -- Ooi, Siew-Eng -- Kok, Sau-Yee -- Sarpan, Norashikin -- Azimi, Nuraziyan -- Hashim, Ahmad Tarmizi -- Ishak, Zamzuri -- Rosli, Samsul Kamal -- Malike, Fadila Ahmad -- Bakar, Nor Azwani Abu -- Marjuni, Marhalil -- Abdullah, Norziha -- Yaakub, Zulkifli -- Amiruddin, Mohd Din -- Nookiah, Rajanaidu -- Singh, Rajinder -- Low, Eng-Ti Leslie -- Chan, Kuang-Lim -- Azizi, Norazah -- Smith, Steven W -- Bacher, Blaire -- Budiman, Muhammad A -- Van Brunt, Andrew -- Wischmeyer, Corey -- Beil, Melissa -- Hogan, Michael -- Lakey, Nathan -- Lim, Chin-Ching -- Arulandoo, Xaviar -- Wong, Choo-Kien -- Choo, Chin-Nee -- Wong, Wei-Chee -- Kwan, Yen-Yen -- Alwee, Sharifah Shahrul Rabiah Syed -- Sambanthamurthi, Ravigadevi -- Martienssen, Robert A -- R01 GM067014/GM/NIGMS NIH HHS/ -- England -- Nature. 2015 Sep 24;525(7570):533-7. doi: 10.1038/nature15365. Epub 2015 Sep 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Malaysian Palm Oil Board, 6, Persiaran Institusi, Bandar Baru Bangi, 43000 Kajang, Selangor, Malaysia. ; Orion Genomics, 4041 Forest Park Avenue, St Louis, Missouri 63108, USA. ; United Plantations Berhad, Jendarata Estate, 36009 Teluk Intan, Perak, Malaysia. ; Applied Agricultural Resources Sdn Bhd, No. 11, Jalan Teknologi 3/6, Taman Sains Selangor 1, 47810 Kota Damansara, Petaling Jaya, Selangor, Malaysia. ; FELDA Global Ventures R&D Sdn Bhd, c/o FELDA Biotechnology Centre, PT 23417, Lengkuk Teknologi, 71760 Bandar Enstek, Negeri Sembilan, Malaysia. ; Howard Hughes Medical Institute-Gordon and Betty Moore Foundation, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26352475" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Alternative Splicing/genetics ; Arecaceae/*genetics/metabolism ; *DNA Methylation ; Epigenesis, Genetic/*genetics ; *Epigenomics ; Fruit/genetics ; Genes, Homeobox/genetics ; Genetic Association Studies ; Genome, Plant/*genetics ; Introns/genetics ; Molecular Sequence Data ; *Phenotype ; Plant Oils/analysis/metabolism ; RNA Splice Sites/genetics ; RNA, Small Interfering/genetics ; Retroelements/*genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Publication Date: 2012-08-24
    Description: Mutations generate sequence diversity and provide a substrate for selection. The rate of de novo mutations is therefore of major importance to evolution. Here we conduct a study of genome-wide mutation rates by sequencing the entire genomes of 78 Icelandic parent-offspring trios at high coverage. We show that in our samples, with an average father's age of 29.7, the average de novo mutation rate is 1.20 x 10(-8) per nucleotide per generation. Most notably, the diversity in mutation rate of single nucleotide polymorphisms is dominated by the age of the father at conception of the child. The effect is an increase of about two mutations per year. An exponential model estimates paternal mutations doubling every 16.5 years. After accounting for random Poisson variation, father's age is estimated to explain nearly all of the remaining variation in the de novo mutation counts. These observations shed light on the importance of the father's age on the risk of diseases such as schizophrenia and autism.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3548427/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3548427/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kong, Augustine -- Frigge, Michael L -- Masson, Gisli -- Besenbacher, Soren -- Sulem, Patrick -- Magnusson, Gisli -- Gudjonsson, Sigurjon A -- Sigurdsson, Asgeir -- Jonasdottir, Aslaug -- Jonasdottir, Adalbjorg -- Wong, Wendy S W -- Sigurdsson, Gunnar -- Walters, G Bragi -- Steinberg, Stacy -- Helgason, Hannes -- Thorleifsson, Gudmar -- Gudbjartsson, Daniel F -- Helgason, Agnar -- Magnusson, Olafur Th -- Thorsteinsdottir, Unnur -- Stefansson, Kari -- MH071425/MH/NIMH NIH HHS/ -- R01 MH071425/MH/NIMH NIH HHS/ -- England -- Nature. 2012 Aug 23;488(7412):471-5. doi: 10.1038/nature11396.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉deCODE Genetics, Sturlugata 8, 101 Reykjavik, Iceland. kong@decode.is〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22914163" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Autistic Disorder/epidemiology/etiology/*genetics ; Chromosomes, Human/genetics ; Female ; *Genetic Predisposition to Disease ; Genome, Human/genetics ; Humans ; Iceland/epidemiology ; Male ; Middle Aged ; Mothers ; *Mutation Rate ; Ovum/metabolism ; *Paternal Age ; Pedigree ; Polymorphism, Single Nucleotide/genetics ; Risk Factors ; Schizophrenia/epidemiology/etiology/*genetics ; Selection, Genetic/genetics ; Sequence Analysis, DNA ; Spermatozoa/metabolism ; Young Adult
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Publication Date: 2012-12-04
    Description: Although initially viewed as unregulated, increasing evidence suggests that cellular necrosis often proceeds through a specific molecular program. In particular, death ligands such as tumour necrosis factor (TNF)-alpha activate necrosis by stimulating the formation of a complex containing receptor-interacting protein 1 (RIP1) and receptor-interacting protein 3 (RIP3). Relatively little is known regarding how this complex formation is regulated. Here, we show that the NAD-dependent deacetylase SIRT2 binds constitutively to RIP3 and that deletion or knockdown of SIRT2 prevents formation of the RIP1-RIP3 complex in mice. Furthermore, genetic or pharmacological inhibition of SIRT2 blocks cellular necrosis induced by TNF-alpha. We further demonstrate that RIP1 is a critical target of SIRT2-dependent deacetylation. Using gain- and loss-of-function mutants, we demonstrate that acetylation of RIP1 lysine 530 modulates RIP1-RIP3 complex formation and TNF-alpha-stimulated necrosis. In the setting of ischaemia-reperfusion injury, RIP1 is deacetylated in a SIRT2-dependent fashion. Furthermore, the hearts of Sirt2(-/-) mice, or wild-type mice treated with a specific pharmacological inhibitor of SIRT2, show marked protection from ischaemic injury. Taken together, these results implicate SIRT2 as an important regulator of programmed necrosis and indicate that inhibitors of this deacetylase may constitute a novel approach to protect against necrotic injuries, including ischaemic stroke and myocardial infarction.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Narayan, Nisha -- Lee, In Hye -- Borenstein, Ronen -- Sun, Junhui -- Wong, Renee -- Tong, Guang -- Fergusson, Maria M -- Liu, Jie -- Rovira, Ilsa I -- Cheng, Hwei-Ling -- Wang, Guanghui -- Gucek, Marjan -- Lombard, David -- Alt, Fredrick W -- Sack, Michael N -- Murphy, Elizabeth -- Cao, Liu -- Finkel, Toren -- Intramural NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Dec 13;492(7428):199-204. doi: 10.1038/nature11700. Epub 2012 Nov 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Molecular Medicine, National Heart, Lung and Blood Institute, NIH, Bethesda, Maryland 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23201684" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Animals ; Cell Line ; Female ; HEK293 Cells ; HeLa Cells ; Humans ; Jurkat Cells ; Male ; Mice ; Necrosis/*enzymology ; Nuclear Pore Complex Proteins/metabolism ; Protein Binding ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism ; Sirtuin 2/*genetics/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    Publication Date: 2015-08-27
    Description: The GGGGCC (G4C2) repeat expansion in a noncoding region of C9orf72 is the most common cause of sporadic and familial forms of amyotrophic lateral sclerosis and frontotemporal dementia. The basis for pathogenesis is unknown. To elucidate the consequences of G4C2 repeat expansion in a tractable genetic system, we generated transgenic fly lines expressing 8, 28 or 58 G4C2-repeat-containing transcripts that do not have a translation start site (AUG) but contain an open-reading frame for green fluorescent protein to detect repeat-associated non-AUG (RAN) translation. We show that these transgenic animals display dosage-dependent, repeat-length-dependent degeneration in neuronal tissues and RAN translation of dipeptide repeat (DPR) proteins, as observed in patients with C9orf72-related disease. This model was used in a large-scale, unbiased genetic screen, ultimately leading to the identification of 18 genetic modifiers that encode components of the nuclear pore complex (NPC), as well as the machinery that coordinates the export of nuclear RNA and the import of nuclear proteins. Consistent with these results, we found morphological abnormalities in the architecture of the nuclear envelope in cells expressing expanded G4C2 repeats in vitro and in vivo. Moreover, we identified a substantial defect in RNA export resulting in retention of RNA in the nuclei of Drosophila cells expressing expanded G4C2 repeats and also in mammalian cells, including aged induced pluripotent stem-cell-derived neurons from patients with C9orf72-related disease. These studies show that a primary consequence of G4C2 repeat expansion is the compromise of nucleocytoplasmic transport through the nuclear pore, revealing a novel mechanism of neurodegeneration.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4631399/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4631399/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Freibaum, Brian D -- Lu, Yubing -- Lopez-Gonzalez, Rodrigo -- Kim, Nam Chul -- Almeida, Sandra -- Lee, Kyung-Ha -- Badders, Nisha -- Valentine, Marc -- Miller, Bruce L -- Wong, Philip C -- Petrucelli, Leonard -- Kim, Hong Joo -- Gao, Fen-Biao -- Taylor, J Paul -- AG019724/AG/NIA NIH HHS/ -- N079725/PHS HHS/ -- NS079725/NS/NINDS NIH HHS/ -- P01 AG019724/AG/NIA NIH HHS/ -- R01 NS057553/NS/NINDS NIH HHS/ -- R01 NS079725/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2015 Sep 3;525(7567):129-33. doi: 10.1038/nature14974. Epub 2015 Aug 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell and Molecular Biology, St Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. ; Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA. ; Memory and Aging Center, Department of Neurology, University of California San Francisco, San Francisco, California 94158, USA. ; Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. ; Department of Neuroscience, Mayo Clinic Florida, Jacksonville, Florida 32224, USA. ; Howard Hughes Medical Institute, Department of Cell and Molecular Biology, St Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26308899" target="_blank"〉PubMed〈/a〉
    Keywords: Active Transport, Cell Nucleus/*genetics ; Amyotrophic Lateral Sclerosis/genetics/pathology ; Animals ; Animals, Genetically Modified ; DNA Repeat Expansion/*genetics ; Drosophila melanogaster/*cytology/genetics/*metabolism ; Eye/metabolism ; Female ; Frontotemporal Dementia/genetics/pathology ; HeLa Cells ; Humans ; Induced Pluripotent Stem Cells/cytology/metabolism ; Male ; Muscles/cytology/metabolism ; Neurons/cytology/metabolism ; Nuclear Pore/genetics/metabolism/pathology ; Open Reading Frames/*genetics ; Phenotype ; Protein Biosynthesis ; Proteins/*genetics ; RNA/genetics/metabolism ; RNA Transport/*genetics ; Salivary Glands/cytology/metabolism/pathology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    Publication Date: 2015-02-25
    Description: Immunoglobulin E (IgE) is a central mediator of allergic (atopic) inflammation. Therapies directed against IgE can alleviate hay fever and allergic asthma. Genetic association studies have not yet identified novel therapeutic targets or pathways underlying IgE regulation. We therefore surveyed epigenetic associations between serum IgE concentrations and methylation at loci concentrated in CpG islands genome wide in 95 nuclear pedigrees, using DNA from peripheral blood leukocytes. We validated positive results in additional families and in subjects from the general population. Here we show replicated associations--with a meta-analysis false discovery rate less than 10(-4)--between IgE and low methylation at 36 loci. Genes annotated to these loci encode known eosinophil products, and also implicate phospholipid inflammatory mediators, specific transcription factors and mitochondrial proteins. We confirmed that methylation at these loci differed significantly in isolated eosinophils from subjects with and without asthma and high IgE levels. The top three loci accounted for 13% of IgE variation in the primary subject panel, explaining the tenfold higher variance found compared with that derived from large single-nucleotide polymorphism genome-wide association studies. This study identifies novel therapeutic targets and biomarkers for patient stratification for allergic diseases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4416961/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4416961/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liang, Liming -- Willis-Owen, Saffron A G -- Laprise, Catherine -- Wong, Kenny C C -- Davies, Gwyneth A -- Hudson, Thomas J -- Binia, Aristea -- Hopkin, Julian M -- Yang, Ivana V -- Grundberg, Elin -- Busche, Stephan -- Hudson, Marie -- Ronnblom, Lars -- Pastinen, Tomi M -- Schwartz, David A -- Lathrop, G Mark -- Moffatt, Miriam F -- Cookson, William O C M -- 096964/Wellcome Trust/United Kingdom -- 097117/Wellcome Trust/United Kingdom -- P01-ES18181/ES/NIEHS NIH HHS/ -- R01 HL101251-01/HL/NHLBI NIH HHS/ -- WT 077959/Wellcome Trust/United Kingdom -- WT096964/Wellcome Trust/United Kingdom -- Medical Research Council/United Kingdom -- England -- Nature. 2015 Apr 30;520(7549):670-4. doi: 10.1038/nature14125. Epub 2015 Feb 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Epidemiology and Biostatistics, Harvard School of Public Health, Boston, Massachusetts 02115, USA. ; National Heart and Lung Institute, Imperial College, London SW3 6LY, UK. ; Universite du Quebec a Chicoutimi, Saguenay, Quebec G7H 2B1, Canada. ; Institute of Life Science, College of Medicine, Swansea University, Swansea SA2 8PP, UK. ; 1] Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada [2] Departments of Medical Biophysics and Molecular Genetics, University of Toronto, Ontario M5S 1A1, Canada. ; University of Colorado School of Medicine and National Jewish Health, Denver, Colorado 80206, USA. ; Department of Human Genetics, McGill University and Genome Quebec Innovation Centre, Montreal H3A 1B1, Canada. ; Jewish General Hospital and Lady Davis Research Institute, Montreal H3T 1E2, Canada. ; Department of Medical Sciences, SciLifeLab, Uppsala University, Uppsala SE-751 44, Sweden. ; 1] Department of Human Genetics, McGill University and Genome Quebec Innovation Centre, Montreal H3A 1B1, Canada [2] Department of Medical Genetics, McGill University Health Centre, Montreal H3H 1P3, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25707804" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; Asthma/blood/genetics ; Child ; CpG Islands/genetics ; DNA Methylation/*genetics ; Eosinophils/cytology/metabolism ; Epigenesis, Genetic/*genetics ; Female ; *Genetic Association Studies ; Genome, Human/*genetics ; Humans ; Immunoglobulin E/*blood ; Inflammation Mediators ; Male ; Middle Aged ; Mitochondrial Proteins/genetics ; Pedigree ; Polymorphism, Single Nucleotide/genetics ; Transcription Factors/genetics ; Young Adult
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    Publication Date: 2015-02-13
    Description: Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P 〈 5 x 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for approximately 2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for 〉20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4382211/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4382211/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Locke, Adam E -- Kahali, Bratati -- Berndt, Sonja I -- Justice, Anne E -- Pers, Tune H -- Day, Felix R -- Powell, Corey -- Vedantam, Sailaja -- Buchkovich, Martin L -- Yang, Jian -- Croteau-Chonka, Damien C -- Esko, Tonu -- Fall, Tove -- Ferreira, Teresa -- Gustafsson, Stefan -- Kutalik, Zoltan -- Luan, Jian'an -- Magi, Reedik -- Randall, Joshua C -- Winkler, Thomas W -- Wood, Andrew R -- Workalemahu, Tsegaselassie -- Faul, Jessica D -- Smith, Jennifer A -- Hua Zhao, Jing -- Zhao, Wei -- Chen, Jin -- Fehrmann, Rudolf -- Hedman, Asa K -- Karjalainen, Juha -- Schmidt, Ellen M -- Absher, Devin -- Amin, Najaf -- Anderson, Denise -- Beekman, Marian -- Bolton, Jennifer L -- Bragg-Gresham, Jennifer L -- Buyske, Steven -- Demirkan, Ayse -- Deng, Guohong -- Ehret, Georg B -- Feenstra, Bjarke -- Feitosa, Mary F -- Fischer, Krista -- Goel, Anuj -- Gong, Jian -- Jackson, Anne U -- Kanoni, Stavroula -- Kleber, Marcus E -- Kristiansson, Kati -- Lim, Unhee -- Lotay, Vaneet -- Mangino, Massimo -- Mateo Leach, Irene -- Medina-Gomez, Carolina -- Medland, Sarah E -- Nalls, Michael A -- Palmer, Cameron D -- Pasko, Dorota -- Pechlivanis, Sonali -- Peters, Marjolein J -- Prokopenko, Inga -- Shungin, Dmitry -- Stancakova, Alena -- Strawbridge, Rona J -- Ju Sung, Yun -- Tanaka, Toshiko -- Teumer, Alexander -- Trompet, Stella -- van der Laan, Sander W -- van Setten, Jessica -- Van Vliet-Ostaptchouk, Jana V -- Wang, Zhaoming -- Yengo, Loic -- Zhang, Weihua -- Isaacs, Aaron -- Albrecht, Eva -- Arnlov, Johan -- Arscott, Gillian M -- Attwood, Antony P -- Bandinelli, Stefania -- Barrett, Amy -- Bas, Isabelita N -- Bellis, Claire -- Bennett, Amanda J -- Berne, Christian -- Blagieva, Roza -- Bluher, Matthias -- Bohringer, Stefan -- Bonnycastle, Lori L -- Bottcher, Yvonne -- Boyd, Heather A -- Bruinenberg, Marcel -- Caspersen, Ida H -- Ida Chen, Yii-Der -- Clarke, Robert -- Daw, E Warwick -- de Craen, Anton J M -- Delgado, Graciela -- Dimitriou, Maria -- Doney, Alex S F -- Eklund, Niina -- Estrada, Karol -- Eury, Elodie -- Folkersen, Lasse -- Fraser, Ross M -- Garcia, Melissa E -- Geller, Frank -- Giedraitis, Vilmantas -- Gigante, Bruna -- Go, Alan S -- Golay, Alain -- Goodall, Alison H -- Gordon, Scott D -- Gorski, Mathias -- Grabe, Hans-Jorgen -- Grallert, Harald -- Grammer, Tanja B -- Grassler, Jurgen -- Gronberg, Henrik -- Groves, Christopher J -- Gusto, Gaelle -- Haessler, Jeffrey -- Hall, Per -- Haller, Toomas -- Hallmans, Goran -- Hartman, Catharina A -- Hassinen, Maija -- Hayward, Caroline -- Heard-Costa, Nancy L -- Helmer, Quinta -- Hengstenberg, Christian -- Holmen, Oddgeir -- Hottenga, Jouke-Jan -- James, Alan L -- Jeff, Janina M -- Johansson, Asa -- Jolley, Jennifer -- Juliusdottir, Thorhildur -- Kinnunen, Leena -- Koenig, Wolfgang -- Koskenvuo, Markku -- Kratzer, Wolfgang -- Laitinen, Jaana -- Lamina, Claudia -- Leander, Karin -- Lee, Nanette R -- Lichtner, Peter -- Lind, Lars -- Lindstrom, Jaana -- Sin Lo, Ken -- Lobbens, Stephane -- Lorbeer, Roberto -- Lu, Yingchang -- Mach, Francois -- Magnusson, Patrik K E -- Mahajan, Anubha -- McArdle, Wendy L -- McLachlan, Stela -- Menni, Cristina -- Merger, Sigrun -- Mihailov, Evelin -- Milani, Lili -- Moayyeri, Alireza -- Monda, Keri L -- Morken, Mario A -- Mulas, Antonella -- Muller, Gabriele -- Muller-Nurasyid, Martina -- Musk, Arthur W -- Nagaraja, Ramaiah -- Nothen, Markus M -- Nolte, Ilja M -- Pilz, Stefan -- Rayner, Nigel W -- Renstrom, Frida -- Rettig, Rainer -- Ried, Janina S -- Ripke, Stephan -- Robertson, Neil R -- Rose, Lynda M -- Sanna, Serena -- Scharnagl, Hubert -- Scholtens, Salome -- Schumacher, Fredrick R -- Scott, William R -- Seufferlein, Thomas -- Shi, Jianxin -- Vernon Smith, Albert -- Smolonska, Joanna -- Stanton, Alice V -- Steinthorsdottir, Valgerdur -- Stirrups, Kathleen -- Stringham, Heather M -- Sundstrom, Johan -- Swertz, Morris A -- Swift, Amy J -- Syvanen, Ann-Christine -- Tan, Sian-Tsung -- Tayo, Bamidele O -- Thorand, Barbara -- Thorleifsson, Gudmar -- Tyrer, Jonathan P -- Uh, Hae-Won -- Vandenput, Liesbeth -- Verhulst, Frank C -- Vermeulen, Sita H -- Verweij, Niek -- Vonk, Judith M -- Waite, Lindsay L -- Warren, Helen R -- Waterworth, Dawn -- Weedon, Michael N -- Wilkens, Lynne R -- Willenborg, Christina -- Wilsgaard, Tom -- Wojczynski, Mary K -- Wong, Andrew -- Wright, Alan F -- Zhang, Qunyuan -- LifeLines Cohort Study -- Brennan, Eoin P -- Choi, Murim -- Dastani, Zari -- Drong, Alexander W -- Eriksson, Per -- Franco-Cereceda, Anders -- Gadin, Jesper R -- Gharavi, Ali G -- Goddard, Michael E -- Handsaker, Robert E -- Huang, Jinyan -- Karpe, Fredrik -- Kathiresan, Sekar -- Keildson, Sarah -- Kiryluk, Krzysztof -- Kubo, Michiaki -- Lee, Jong-Young -- Liang, Liming -- Lifton, Richard P -- Ma, Baoshan -- McCarroll, Steven A -- McKnight, Amy J -- Min, Josine L -- Moffatt, Miriam F -- Montgomery, Grant W -- Murabito, Joanne M -- Nicholson, George -- Nyholt, Dale R -- Okada, Yukinori -- Perry, John R B -- Dorajoo, Rajkumar -- Reinmaa, Eva -- Salem, Rany M -- Sandholm, Niina -- Scott, Robert A -- Stolk, Lisette -- Takahashi, Atsushi -- Tanaka, Toshihiro -- Van't Hooft, Ferdinand M -- Vinkhuyzen, Anna A E -- Westra, Harm-Jan -- Zheng, Wei -- Zondervan, Krina T -- ADIPOGen Consortium -- AGEN-BMI Working Group -- CARDIOGRAMplusC4D Consortium -- CKDGen Consortium -- GLGC -- ICBP -- MAGIC Investigators -- MuTHER Consortium -- MIGen Consortium -- PAGE Consortium -- ReproGen Consortium -- GENIE Consortium -- International Endogene Consortium -- Heath, Andrew C -- Arveiler, Dominique -- Bakker, Stephan J L -- Beilby, John -- Bergman, Richard N -- Blangero, John -- Bovet, Pascal -- Campbell, Harry -- Caulfield, Mark J -- Cesana, Giancarlo -- Chakravarti, Aravinda -- Chasman, Daniel I -- Chines, Peter S -- Collins, Francis S -- Crawford, Dana C -- Cupples, L Adrienne -- Cusi, Daniele -- Danesh, John -- de Faire, Ulf -- den Ruijter, Hester M -- Dominiczak, Anna F -- Erbel, Raimund -- Erdmann, Jeanette -- Eriksson, Johan G -- Farrall, Martin -- Felix, Stephan B -- Ferrannini, Ele -- Ferrieres, Jean -- Ford, Ian -- Forouhi, Nita G -- Forrester, Terrence -- Franco, Oscar H -- Gansevoort, Ron T -- Gejman, Pablo V -- Gieger, Christian -- Gottesman, Omri -- Gudnason, Vilmundur -- Gyllensten, Ulf -- Hall, Alistair S -- Harris, Tamara B -- Hattersley, Andrew T -- Hicks, Andrew A -- Hindorff, Lucia A -- Hingorani, Aroon D -- Hofman, Albert -- Homuth, Georg -- Hovingh, G Kees -- Humphries, Steve E -- Hunt, Steven C -- Hypponen, Elina -- Illig, Thomas -- Jacobs, Kevin B -- Jarvelin, Marjo-Riitta -- Jockel, Karl-Heinz -- Johansen, Berit -- Jousilahti, Pekka -- Jukema, J Wouter -- Jula, Antti M -- Kaprio, Jaakko -- Kastelein, John J P -- Keinanen-Kiukaanniemi, Sirkka M -- Kiemeney, Lambertus A -- Knekt, Paul -- Kooner, Jaspal S -- Kooperberg, Charles -- Kovacs, Peter -- Kraja, Aldi T -- Kumari, Meena -- Kuusisto, Johanna -- Lakka, Timo A -- Langenberg, Claudia -- Le Marchand, Loic -- Lehtimaki, Terho -- Lyssenko, Valeriya -- Mannisto, Satu -- Marette, Andre -- Matise, Tara C -- McKenzie, Colin A -- McKnight, Barbara -- Moll, Frans L -- Morris, Andrew D -- Morris, Andrew P -- Murray, Jeffrey C -- Nelis, Mari -- Ohlsson, Claes -- Oldehinkel, Albertine J -- Ong, Ken K -- Madden, Pamela A F -- Pasterkamp, Gerard -- Peden, John F -- Peters, Annette -- Postma, Dirkje S -- Pramstaller, Peter P -- Price, Jackie F -- Qi, Lu -- Raitakari, Olli T -- Rankinen, Tuomo -- Rao, D C -- Rice, Treva K -- Ridker, Paul M -- Rioux, John D -- Ritchie, Marylyn D -- Rudan, Igor -- Salomaa, Veikko -- Samani, Nilesh J -- Saramies, Jouko -- Sarzynski, Mark A -- Schunkert, Heribert -- Schwarz, Peter E H -- Sever, Peter -- Shuldiner, Alan R -- Sinisalo, Juha -- Stolk, Ronald P -- Strauch, Konstantin -- Tonjes, Anke -- Tregouet, David-Alexandre -- Tremblay, Angelo -- Tremoli, Elena -- Virtamo, Jarmo -- Vohl, Marie-Claude -- Volker, Uwe -- Waeber, Gerard -- Willemsen, Gonneke -- Witteman, Jacqueline C -- Zillikens, M Carola -- Adair, Linda S -- Amouyel, Philippe -- Asselbergs, Folkert W -- Assimes, Themistocles L -- Bochud, Murielle -- Boehm, Bernhard O -- Boerwinkle, Eric -- Bornstein, Stefan R -- Bottinger, Erwin P -- Bouchard, Claude -- Cauchi, Stephane -- Chambers, John C -- Chanock, Stephen J -- Cooper, Richard S -- de Bakker, Paul I W -- Dedoussis, George -- Ferrucci, Luigi -- Franks, Paul W -- Froguel, Philippe -- Groop, Leif C -- Haiman, Christopher A -- Hamsten, Anders -- Hui, Jennie -- Hunter, David J -- Hveem, Kristian -- Kaplan, Robert C -- Kivimaki, Mika -- Kuh, Diana -- Laakso, Markku -- Liu, Yongmei -- Martin, Nicholas G -- Marz, Winfried -- Melbye, Mads -- Metspalu, Andres -- Moebus, Susanne -- Munroe, Patricia B -- Njolstad, Inger -- Oostra, Ben A -- Palmer, Colin N A -- Pedersen, Nancy L -- Perola, Markus -- Perusse, Louis -- Peters, Ulrike -- Power, Chris -- Quertermous, Thomas -- Rauramaa, Rainer -- Rivadeneira, Fernando -- Saaristo, Timo E -- Saleheen, Danish -- Sattar, Naveed -- Schadt, Eric E -- Schlessinger, David -- Slagboom, P Eline -- Snieder, Harold -- Spector, Tim D -- Thorsteinsdottir, Unnur -- Stumvoll, Michael -- Tuomilehto, Jaakko -- Uitterlinden, Andre G -- Uusitupa, Matti -- van der Harst, Pim -- Walker, Mark -- Wallaschofski, Henri -- Wareham, Nicholas J -- Watkins, Hugh -- Weir, David R -- Wichmann, H-Erich -- Wilson, James F -- Zanen, Pieter -- Borecki, Ingrid B -- Deloukas, Panos -- Fox, Caroline S -- Heid, Iris M -- O'Connell, Jeffrey R -- Strachan, David P -- Stefansson, Kari -- van Duijn, Cornelia M -- Abecasis, Goncalo R -- Franke, Lude -- Frayling, Timothy M -- McCarthy, Mark I -- Visscher, Peter M -- Scherag, Andre -- Willer, Cristen J -- Boehnke, Michael -- Mohlke, Karen L -- Lindgren, Cecilia M -- Beckmann, Jacques S -- Barroso, Ines -- North, Kari E -- Ingelsson, Erik -- Hirschhorn, Joel N -- Loos, Ruth J F -- Speliotes, Elizabeth K -- 084766/Wellcome Trust/United Kingdom -- 085235/Wellcome Trust/United Kingdom -- 097117/Wellcome Trust/United Kingdom -- 098381/Wellcome Trust/United Kingdom -- 14136/Cancer Research UK/United Kingdom -- CZB/4/672/Chief Scientist Office/United Kingdom -- CZB/4/710/Chief Scientist Office/United Kingdom -- G0601261/Medical Research Council/United Kingdom -- G1000143/Medical Research Council/United Kingdom -- K01 HL116770/HL/NHLBI NIH HHS/ -- K23 DK080145/DK/NIDDK NIH HHS/ -- MC_PC_U127561128/Medical Research Council/United Kingdom -- MC_U106179471/Medical Research Council/United Kingdom -- MC_UU_12015/1/Medical Research Council/United Kingdom -- MC_UU_12015/2/Medical Research Council/United Kingdom -- MC_UU_12015/5/Medical Research Council/United Kingdom -- MR/K013351/1/Medical Research Council/United Kingdom -- P20 MD006899/MD/NIMHD NIH HHS/ -- P30 DK020541/DK/NIDDK NIH HHS/ -- P30 DK020572/DK/NIDDK NIH HHS/ -- P30 DK063491/DK/NIDDK NIH HHS/ -- P30 GM103341/GM/NIGMS NIH HHS/ -- P30 HL107251/HL/NHLBI NIH HHS/ -- P60 DK020541/DK/NIDDK NIH HHS/ -- R01 AG041517/AG/NIA NIH HHS/ -- R01 DK062370/DK/NIDDK NIH HHS/ -- R01 DK072193/DK/NIDDK NIH HHS/ -- R01 DK075787/DK/NIDDK NIH HHS/ -- R01 DK078150/DK/NIDDK NIH HHS/ -- R01 DK089256/DK/NIDDK NIH HHS/ -- R01 DK093757/DK/NIDDK NIH HHS/ -- R01 HL109946/HL/NHLBI NIH HHS/ -- R01 HL117626/HL/NHLBI NIH HHS/ -- R21 DA027040/DA/NIDA NIH HHS/ -- T32 GM080178/GM/NIGMS NIH HHS/ -- T32 HL007055/HL/NHLBI NIH HHS/ -- T32 HL007824/HL/NHLBI NIH HHS/ -- TL1 TR001066/TR/NCATS NIH HHS/ -- U01 AG009740/AG/NIA NIH HHS/ -- U01 AG049505/AG/NIA NIH HHS/ -- U01 DK062370/DK/NIDDK NIH HHS/ -- U01 HG007416/HG/NHGRI NIH HHS/ -- U01 HG007419/HG/NHGRI NIH HHS/ -- UL1 TR000124/TR/NCATS NIH HHS/ -- UL1 TR001067/TR/NCATS NIH HHS/ -- UM1 CA182910/CA/NCI NIH HHS/ -- England -- Nature. 2015 Feb 12;518(7538):197-206. doi: 10.1038/nature14177.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan 48109, USA. ; Department of Internal Medicine, Division of Gastroenterology, and Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 48109, USA. ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. ; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA. ; 1] Divisions of Endocrinology and Genetics and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts 02115, USA. [2] Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA. [3] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA. [4] Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby 2800, Denmark. ; MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK. ; 1] Divisions of Endocrinology and Genetics and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts 02115, USA. [2] Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA. ; Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599, USA. ; 1] Queensland Brain Institute, The University of Queensland, Brisbane 4072, Australia. [2] The University of Queensland Diamantina Institute, The Translation Research Institute, Brisbane 4012, Australia. ; 1] Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599, USA. [2] Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. ; 1] Divisions of Endocrinology and Genetics and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts 02115, USA. [2] Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA. [3] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA. [4] Estonian Genome Center, University of Tartu, Tartu 51010, Estonia. ; 1] Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm 17177, Sweden. [2] Science for Life Laboratory, Uppsala University, Uppsala 75185, Sweden. [3] Department of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala 75185, Sweden. ; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. ; 1] Science for Life Laboratory, Uppsala University, Uppsala 75185, Sweden. [2] Department of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala 75185, Sweden. ; 1] Institute of Social and Preventive Medicine (IUMSP), Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne 1010, Switzerland. [2] Swiss Institute of Bioinformatics, Lausanne 1015, Switzerland. [3] Department of Medical Genetics, University of Lausanne, Lausanne 1005, Switzerland. ; 1] Estonian Genome Center, University of Tartu, Tartu 51010, Estonia. [2] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. ; 1] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. [2] Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK. ; Department of Genetic Epidemiology, Institute of Epidemiology and Preventive Medicine, University of Regensburg, D-93053 Regensburg, Germany. ; Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter EX1 2LU, UK. ; Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts 02115, USA. ; Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, Michigan 48104, USA. ; Department of Epidemiology, University of Michigan, Ann Arbor, Michigan 48109, USA. ; Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA. ; Department of Genetics, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands. ; 1] Science for Life Laboratory, Uppsala University, Uppsala 75185, Sweden. [2] Department of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala 75185, Sweden. [3] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. ; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 48109, USA. ; HudsonAlpha Institute for Biotechnology, Huntsville, Alabama 35806, USA. ; Genetic Epidemiology Unit, Department of Epidemiology, Erasmus MC University Medical Center, 3015 GE Rotterdam, The Netherlands. ; Telethon Institute for Child Health Research, Centre for Child Health Research, The University of Western Australia, Perth, Western Australia 6008, Australia. ; 1] Netherlands Consortium for Healthy Aging (NCHA), Leiden University Medical Center, Leiden 2300 RC, The Netherlands. [2] Department of Molecular Epidemiology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. ; Centre for Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG, UK. ; 1] Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan 48109, USA. [2] Kidney Epidemiology and Cost Center, University of Michigan, Ann Arbor, Michigan 48109, USA. ; 1] Department of Statistics &Biostatistics, Rutgers University, Piscataway, New Jersey 08854, USA. [2] Department of Genetics, Rutgers University, Piscataway, New Jersey 08854, USA. ; 1] Genetic Epidemiology Unit, Department of Epidemiology, Erasmus MC University Medical Center, 3015 GE Rotterdam, The Netherlands. [2] Department of Human Genetics, Leiden University Medical Center, 2333 ZC Leiden, The Netherlands. ; 1] Ealing Hospital NHS Trust, Middlesex UB1 3HW, UK. [2] Department of Gastroenterology and Hepatology, Imperial College London, London W2 1PG, UK. [3] Institute of infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing, China. ; 1] Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. [2] Cardiology, Department of Specialties of Internal Medicine, Geneva University Hospital, Geneva 1211, Switzerland. ; Department of Epidemiology Research, Statens Serum Institut, Copenhagen DK-2300, Denmark. ; Department of Genetics, Washington University School of Medicine, St Louis, Missouri 63110, USA. ; Estonian Genome Center, University of Tartu, Tartu 51010, Estonia. ; 1] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. [2] Division of Cardiovacular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DU, UK. ; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA. ; William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK. ; 1] Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty of Mannheim, University of Heidelberg, D-68187 Mannheim, Germany. [2] Department of Internal Medicine II, Ulm University Medical Centre, D-89081 Ulm, Germany. ; National Institute for Health and Welfare, FI-00271 Helsinki, Finland. ; Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii 96813, USA. ; The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA. ; Department of Twin Research and Genetic Epidemiology, King's College London, London SE1 7EH, UK. ; Department of Cardiology, University Medical Center Groningen, University of Groningen, 9700RB Groningen, The Netherlands. ; 1] Netherlands Consortium for Healthy Aging (NCHA), 3015GE Rotterdam, The Netherlands. [2] Department of Epidemiology, Erasmus MC University Medical Center, 3015GE Rotterdam, The Netherlands. [3] Department of Internal Medicine, Erasmus MC University Medical Center, 3015GE Rotterdam, The Netherlands. ; QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia. ; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA. ; Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), University Hospital Essen, 45147 Essen, Germany. ; 1] Netherlands Consortium for Healthy Aging (NCHA), 3015GE Rotterdam, The Netherlands. [2] Department of Internal Medicine, Erasmus MC University Medical Center, 3015GE Rotterdam, The Netherlands. ; 1] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. [2] Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford OX3 7LJ, UK. [3] Department of Genomics of Common Disease, School of Public Health, Imperial College London, Hammersmith Hospital, London W12 0NN, UK. ; 1] Department of Clinical Sciences, Genetic &Molecular Epidemiology Unit, Lund University Diabetes Center, Skane University Hosptial, Malmo 205 02, Sweden. [2] Department of Public Health and Clinical Medicine, Unit of Medicine, Umea University, Umea 901 87, Sweden. [3] Department of Odontology, Umea University, Umea 901 85, Sweden. ; University of Eastern Finland, FI-70210 Kuopio, Finland. ; Atherosclerosis Research Unit, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Stockholm 17176, Sweden. ; Division of Biostatistics, Washington University School of Medicine, St Louis, Missouri 63110, USA. ; Translational Gerontology Branch, National Institute on Aging, Baltimore, Maryland 21225, USA. ; Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, D-17475 Greifswald, Germany. ; 1] Department of Cardiology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. [2] Department of Gerontology and Geriatrics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. ; Experimental Cardiology Laboratory, Division Heart and Lungs, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands. ; Department of Medical Genetics, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands. ; Department of Endocrinology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands. ; 1] Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. [2] Core Genotyping Facility, SAIC-Frederick, Inc., NCI-Frederick, Frederick, Maryland 21702, USA. ; 1] CNRS UMR 8199, F-59019 Lille, France. [2] European Genomic Institute for Diabetes, F-59000 Lille, France. [3] Universite de Lille 2, F-59000 Lille, France. ; 1] Ealing Hospital NHS Trust, Middlesex UB1 3HW, UK. [2] Department of Epidemiology and Biostatistics, Imperial College London, London W2 1PG, UK. ; 1] Genetic Epidemiology Unit, Department of Epidemiology, Erasmus MC University Medical Center, 3015 GE Rotterdam, The Netherlands. [2] Center for Medical Sytems Biology, 2300 RC Leiden, The Netherlands. ; Institute of Genetic Epidemiology, Helmholtz Zentrum Munchen - German Research Center for Environmental Health, D-85764 Neuherberg, Germany. ; 1] Science for Life Laboratory, Uppsala University, Uppsala 75185, Sweden. [2] Department of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala 75185, Sweden. [3] School of Health and Social Studies, Dalarna University, SE-791 88 Falun, Sweden. ; PathWest Laboratory Medicine of Western Australia, Nedlands, Western Australia 6009, Australia. ; 1] Department of Haematology, University of Cambridge, Cambridge CB2 0PT, UK. [2] NHS Blood and Transplant, Cambridge CB2 0PT, UK. ; Geriatric Unit, Azienda Sanitaria Firenze (ASF), 50125 Florence, Italy. ; Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford OX3 7LJ, UK. ; USC-Office of Population Studies Foundation, Inc., University of San Carlos, Cebu City 6000, Philippines. ; 1] Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas 78227, USA. [2] Genomics Research Centre, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland 4001, Australia. ; Department of Medical Sciences, Endocrinology, Diabetes and Metabolism, Uppsala University, Uppsala 75185, Sweden. ; Division of Endocrinology, Diabetes and Metabolism, Ulm University Medical Centre, D-89081 Ulm, Germany. ; 1] Integrated Research and Treatment Center (IFB) Adiposity Diseases, University of Leipzig, D-04103 Leipzig, Germany. [2] Department of Medicine, University of Leipzig, D-04103 Leipzig, Germany. ; 1] Netherlands Consortium for Healthy Aging (NCHA), Leiden University Medical Center, Leiden 2300 RC, The Netherlands. [2] Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. ; Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland 20892, USA. ; Integrated Research and Treatment Center (IFB) Adiposity Diseases, University of Leipzig, D-04103 Leipzig, Germany. ; LifeLines Cohort Study, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands. ; Department of Biology, Norwegian University of Science and Technology, 7491 Trondheim, Norway. ; 1] Department of Pediatrics, University of California Los Angeles, Torrance, California 90502, USA. [2] Transgenomics Institute, Los Angeles Biomedical Research Institute, Torrance, California 90502, USA. ; Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, UK. ; Department of Gerontology and Geriatrics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. ; Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty of Mannheim, University of Heidelberg, D-68187 Mannheim, Germany. ; Department of Dietetics-Nutrition, Harokopio University, 17671 Athens, Greece. ; Medical Research Institute, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK. ; 1] National Institute for Health and Welfare, FI-00271 Helsinki, Finland. [2] Institute for Molecular Medicine, University of Helsinki, FI-00014 Helsinki, Finland. ; 1] Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA. [2] Department of Internal Medicine, Erasmus MC University Medical Center, 3015GE Rotterdam, The Netherlands. [3] Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. ; Laboratory of Epidemiology and Population Sciences, National Institute on Aging, NIH, Bethesda, Maryland 20892, USA. ; Department of Public Health and Caring Sciences, Geriatrics, Uppsala University, Uppsala 75185, Sweden. ; Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden, Stockholm 17177, Sweden. ; Kaiser Permanente, Division of Research, Oakland, California 94612, USA. ; Service of Therapeutic Education for Diabetes, Obesity and Chronic Diseases, Geneva University Hospital, Geneva CH-1211, Switzerland. ; 1] Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester LE3 9QP, UK. [2] National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester LE3 9QP, UK. ; 1] Department of Genetic Epidemiology, Institute of Epidemiology and Preventive Medicine, University of Regensburg, D-93053 Regensburg, Germany. [2] Department of Nephrology, University Hospital Regensburg, D-93053 Regensburg, Germany. ; 1] Department of Psychiatry and Psychotherapy, University Medicine Greifswald, HELIOS-Hospital Stralsund, D-17475 Greifswald, Germany. [2] German Center for Neurodegenerative Diseases (DZNE), Rostock, Greifswald, D-17475 Greifswald, Germany. ; 1] Institute of Genetic Epidemiology, Helmholtz Zentrum Munchen - German Research Center for Environmental Health, D-85764 Neuherberg, Germany. [2] Research Unit of Molecular Epidemiology, Helmholtz Zentrum Munchen - German Research Center for Environmental Health, D-85764 Neuherberg, Germany. [3] German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany. ; Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universitat Dresden, D-01307 Dresden, Germany. ; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm 17177, Sweden. ; Institut inter Regional pour la Sante, Synergies, F-37520 La Riche, France. ; Department of Public Health and Clinical Medicine, Unit of Nutritional Research, Umea University, Umea 90187, Sweden. ; Department of Psychiatry, University of Groningen, University Medical Center Groningen, 9700RB Groningen, The Netherlands. ; Kuopio Research Institute of Exercise Medicine, 70100 Kuopio, Finland. ; MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK. ; 1] National Heart, Lung, and Blood Institute, the Framingham Heart Study, Framingham, Massachusetts 01702, USA. [2] Department of Neurology, Boston University School of Medicine, Boston, Massachusetts 02118, USA. ; 1] Netherlands Consortium for Healthy Aging (NCHA), Leiden University Medical Center, Leiden 2300 RC, The Netherlands. [2] Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. [3] Faculty of Psychology and Education, VU University Amsterdam, 1081BT Amsterdam, The Netherlands. ; 1] Deutsches Forschungszentrum fur Herz-Kreislauferkrankungen (DZHK) (German Research Centre for Cardiovascular Research), Munich Heart Alliance, D-80636 Munich, Germany. [2] Deutsches Herzzentrum Munchen, Technische Universitat Munchen, D-80636 Munich, Germany. ; Department of Public Health and General Practice, Norwegian University of Science and Technology, Trondheim 7489, Norway. ; Biological Psychology, VU University Amsterdam, 1081BT Amsterdam, The Netherlands. ; 1] Department of Pulmonary Physiology and Sleep Medicine, Nedlands, Western Australia 6009, Australia. [2] School of Medicine and Pharmacology, University of Western Australia, Crawley 6009, Australia. ; Uppsala University, Department of Immunology, Genetics, Pathology, SciLifeLab, Rudbeck Laboratory, SE-751 85 Uppsala, Sweden. ; Department of Internal Medicine II, Ulm University Medical Centre, D-89081 Ulm, Germany. ; Hjelt Institute Department of Public Health, University of Helsinki, FI-00014 Helsinki, Finland. ; Department of Internal Medicine I, Ulm University Medical Centre, D-89081 Ulm, Germany. ; Finnish Institute of Occupational Health, FI-90100 Oulu, Finland. ; Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, 6020 Innsbruck, Austria. ; Institute of Human Genetics, Helmholtz Zentrum Munchen - German Research Center for Environmental Health, D-85764 Neuherberg, Germany. ; Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala 75185, Sweden. ; Montreal Heart Institute, Montreal, Quebec H1T 1C8, Canada. ; Institute for Community Medicine, University Medicine Greifswald, D-17475 Greifswald, Germany. ; 1] The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA. [2] The Genetics of Obesity and Related Metabolic Traits Program, The Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA. ; Cardiology, Department of Specialties of Internal Medicine, Geneva University Hospital, Geneva 1211, Switzerland. ; School of Social and Community Medicine, University of Bristol, Bristol BS8 2BN, UK. ; 1] Estonian Genome Center, University of Tartu, Tartu 51010, Estonia. [2] Institute of Molecular and Cell Biology, University of Tartu, Tartu 51010, Estonia. ; 1] Department of Twin Research and Genetic Epidemiology, King's College London, London SE1 7EH, UK. [2] Farr Institute of Health Informatics Research, University College London, London NW1 2DA, UK. ; 1] Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA. [2] The Center for Observational Research, Amgen, Inc., Thousand Oaks, California 91320, USA. ; Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche, Cagliari, Sardinia 09042, Italy. ; Center for Evidence-based Healthcare, University Hospital Carl Gustav Carus, Technische Universitat Dresden, D-01307 Dresden, Germany. ; 1] Institute of Genetic Epidemiology, Helmholtz Zentrum Munchen - German Research Center for Environmental Health, D-85764 Neuherberg, Germany. [2] Deutsches Forschungszentrum fur Herz-Kreislauferkrankungen (DZHK) (German Research Centre for Cardiovascular Research), Munich Heart Alliance, D-80636 Munich, Germany. [3] Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians-Universitat, D-81377 Munich, Germany. [4] Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-Universitat, D-81377 Munich, Germany. ; Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia 6009, Australia. ; Laboratory of Genetics, National Institute on Aging, Baltimore, Maryland 21224, USA. ; 1] Department of Genomics, Life &Brain Center, University of Bonn, 53127 Bonn, Germany. [2] Institute of Human Genetics, University of Bonn, 53127 Bonn, Germany. ; Department of Epidemiology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands. ; 1] Department of Epidemiology and Biostatistics, Institute for Research in Extramural Medicine, Institute for Health and Care Research, VU University Medical Center, 1081BT Amsterdam, The Netherlands. [2] Department of Internal Medicine, Division of Endocrinology and Metabolism, Medical University of Graz, 8036 Graz, Austria. ; 1] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. [2] Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK. [3] Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford OX3 7LJ, UK. ; Department of Clinical Sciences, Genetic &Molecular Epidemiology Unit, Lund University Diabetes Center, Skane University Hosptial, Malmo 205 02, Sweden. ; Institute of Physiology, University Medicine Greifswald, D-17495 Karlsburg, Germany. ; 1] Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. [2] Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA. ; 1] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. [2] Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford OX3 7LJ, UK. ; Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02215, USA. ; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz 8036, Austria. ; Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA. ; National Cancer Institute, Bethesda, Maryland 20892, USA. ; 1] Icelandic Heart Association, Kopavogur 201, Iceland. [2] University of Iceland, Reykjavik 101, Iceland. ; 1] Department of Genetics, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands. [2] Department of Epidemiology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands. ; Molecular &Cellular Therapeutics, Royal College of Surgeons in Ireland, 123 St Stephen's Green, Dublin 2, Ireland. ; deCODE Genetics, Amgen Inc., Reykjavik 101, Iceland. ; 1] Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK. [2] William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK. ; 1] Science for Life Laboratory, Uppsala University, Uppsala 75185, Sweden. [2] Department of Medical Sciences, Molecular Medicine, Uppsala University, Uppsala 75144, Sweden. ; 1] Ealing Hospital NHS Trust, Middlesex UB1 3HW, UK. [2] National Heart and Lung Institute, Imperial College London, London SW3 6LY, UK. ; Department of Public Health Sciences, Stritch School of Medicine, Loyola University of Chicago, Maywood, Illinois 61053, USA. ; 1] German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany. [2] Institute of Epidemiology II, Helmholtz Zentrum Munchen - German Research Center for Environmental Health, Neuherberg, Germany, D-85764 Neuherberg, Germany. ; Department of Oncology, University of Cambridge, Cambridge CB2 0QQ, UK. ; Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg 413 45, Sweden. ; Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC University Medical Centre, 3000 CB Rotterdam, The Netherlands. ; 1] Department for Health Evidence, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands. [2] Department of Genetics, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands. ; Department of Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK. ; Genetics, GlaxoSmithKline, King of Prussia, Pennsylvania 19406, USA. ; 1] German Center for Cardiovascular Research, partner site Hamburg/Lubeck/Kiel, 23562 Lubeck, Germany. [2] Institut fur Integrative und Experimentelle Genomik, Universitat zu Lubeck, D-23562 Lubeck, Germany. ; Department of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, 9037 Tromso, Norway. ; MRC Unit for Lifelong Health and Ageing at University College London, London WC1B 5JU, UK. ; Diabetes Complications Research Centre, Conway Institute, School of Medicine and Medical Sciences, University College Dublin, Dublin 4, Ireland. ; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea. ; Lady Davis Institute, Departments of Human Genetics, Epidemiology and Biostatistics, McGill University, Montreal, Quebec H3T1E2, Canada. ; Cardiothoracic Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm 17176, Sweden. ; Department of Medicine, Columbia University College of Physicians and Surgeons, New York 10032, USA. ; 1] Biosciences Research Division, Department of Primary Industries, Victoria 3083, Australia. [2] Department of Food and Agricultural Systems, University of Melbourne, Victoria 3010, Australia. ; 1] Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA. [2] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA. ; 1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA. [2] State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China. ; 1] Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford OX3 7LJ, UK. [2] NIHR Oxford Biomedical Research Centre, OUH Trust, Oxford OX3 7LE, UK. ; 1] Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA. [2] Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. ; Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan. ; Center for Genome Science, National Institute of Health, Chungcheongbuk-do, Chungbuk 363-951, Republic of Korea. ; 1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA. [2] Harvard School of Public Health, Department of Biostatistics, Harvard University, Boston, Massachusetts 2115, USA. ; Department of Genetics, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, New Haven, Connecticut 06520, USA. ; 1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA. [2] College of Information Science and Technology, Dalian Maritime University, Dalian, Liaoning 116026, China. ; 1] Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA. [2] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA. [3] Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA. ; Nephrology Research, Centre for Public Health, Queen's University of Belfast, Belfast, County Down BT9 7AB, UK. ; National Heart and Lung Institute, Imperial College London, London SW3 6LY, UK. ; 1] National Heart, Lung, and Blood Institute, the Framingham Heart Study, Framingham, Massachusetts 01702, USA. [2] Section of General Internal Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA. ; 1] Department of Statistics, University of Oxford, 1 South Parks Road, Oxford OX1 3TG, UK. [2] MRC Harwell, Harwell Science and Innovation Campus, Harwell OX11 0QG, UK. ; 1] QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia. [2] Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland 4059, Australia. ; 1] Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan. [2] Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 113-8510 Tokyo, Japan. ; 1] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. [2] Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter EX1 2LU, UK. [3] Department of Twin Research and Genetic Epidemiology, King's College London, London SE1 7EH, UK. ; Genome Institute of Singapore, Agency for Science, Technology and Research, 138672 Singapore. ; 1] Divisions of Endocrinology and Genetics and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts 02115, USA. [2] Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA. [3] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA. ; 1] Department of Biomedical Engineering and Computational Science, Aalto University School of Science, Helsinki FI-00076, Finland. [2] Department of Medicine, Division of Nephrology, Helsinki University Central Hospital, FI-00290 Helsinki, Finland. [3] Folkhalsan Institute of Genetics, Folkhalsan Research Center, FI-00290 Helsinki, Finland. ; 1] Netherlands Consortium for Healthy Aging (NCHA), Leiden University Medical Center, Leiden 2300 RC, The Netherlands. [2] Department of Internal Medicine, Erasmus MC University Medical Center, 3015GE Rotterdam, The Netherlands. ; Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan. ; 1] Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 113-8510 Tokyo, Japan. [2] Laboratory for Cardiovascular Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan. [3] Division of Disease Diversity, Bioresource Research Center, Tokyo Medical and Dental University, 113-8510 Tokyo, Japan. ; Queensland Brain Institute, The University of Queensland, Brisbane 4072, Australia. ; Division of Epidemiology, Department of Medicine; Vanderbilt Epidemiology Center; and Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee 37075, USA. ; 1] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. [2] Nuffield Department of Obstetrics &Gynaecology, University of Oxford, Oxford OX3 7BN, UK. ; Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri 63110, USA. ; Department of Epidemiology and Public Health, EA3430, University of Strasbourg, Faculty of Medicine, Strasbourg, France. ; Department of Internal Medicine, University Medical Center Groningen, University of Groningen, 9700RB Groningen, The Netherlands. ; 1] PathWest Laboratory Medicine of Western Australia, Nedlands, Western Australia 6009, Australia. [2] Pathology and Laboratory Medicine, The University of Western Australia, Perth, Western Australia 6009, Australia. ; Cedars-Sinai Diabetes and Obesity Research Institute, Los Angeles, California 90048, USA. ; Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas 78227, USA. ; 1] Institute of Social and Preventive Medicine (IUMSP), Centre Hospitalier Universitaire Vaudois and University of Lausanne, 1010 Lausanne, Switzerland. [2] Ministry of Health, Victoria, Republic of Seychelles. ; University of Milano, Bicocca, 20126, Italy. ; Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. ; 1] Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02215, USA. [2] Harvard Medical School, Boston, Massachusetts 02115, USA. ; 1] Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, Tennessee 37203, USA. [2] Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee 37232, USA. ; 1] National Heart, Lung, and Blood Institute, the Framingham Heart Study, Framingham, Massachusetts 01702, USA. [2] Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts 02118, USA. ; 1] Department of Health Sciences, University of Milano, I 20142, Italy. [2] Fondazione Filarete, Milano I 20139, Italy. ; Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK. ; 1] Experimental Cardiology Laboratory, Division Heart and Lungs, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands. [2] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands. ; Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK. ; Clinic of Cardiology, West-German Heart Centre, University Hospital Essen, 45147 Essen, Germany. ; 1] National Institute for Health and Welfare, FI-00271 Helsinki, Finland. [2] Department of General Practice and Primary Health Care, University of Helsinki, FI-00290 Helsinki, Finland. [3] Unit of General Practice, Helsinki University Central Hospital, Helsinki 00290, Finland. ; 1] Department of Internal Medicine B, University Medicine Greifswald, D-17475 Greifswald, Germany. [2] DZHK (Deutsches Zentrum fur Herz-Kreislaufforschung - German Centre for Cardiovascular Research), partner site Greifswald, D-17475 Greifswald, Germany. ; 1] Department of Internal Medicine, University of Pisa, 56100 Pisa, Italy. [2] National Research Council Institute of Clinical Physiology, University of Pisa, 56124 Pisa, Italy. ; Department of Cardiology, Toulouse University School of Medicine, Rangueil Hospital, 31400 Toulouse, France. ; Robertson Center for Biostatistics, University of Glasgow, Glasgow G12 8QQ, UK. ; UWI Solutions for Developing Countries, The University of the West Indies, Mona, Kingston 7, Jamaica. ; 1] Netherlands Consortium for Healthy Aging (NCHA), 3015GE Rotterdam, The Netherlands. [2] Department of Epidemiology, Erasmus MC University Medical Center, 3015GE Rotterdam, The Netherlands. ; NorthShore University HealthSystem, Evanston, IL 60201, University of Chicago, Chicago, Illinois, USA. ; Leeds MRC Medical Bioinformatics Centre, University of Leeds, Leeds LS2 9LU, UK. ; Institute of Biomedical &Clinical Science, University of Exeter, Barrack Road, Exeter EX2 5DW, UK. ; Center for Biomedicine, European Academy Bozen, Bolzano (EURAC), Bolzano 39100, Italy (affiliated institute of the University of Lubeck, D-23562 Lubeck, Germany). ; Division of Genomic Medicine, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. ; Institute of Cardiovascular Science, University College London, London WC1E 6BT, UK. ; Department of Vascular Medicine, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands. ; Centre for Cardiovascular Genetics, Institute Cardiovascular Sciences, University College London, London WC1E 6JJ, UK. ; Cardiovascular Genetics Division, Department of Internal Medicine, University of Utah, Salt Lake City, Utah 84108, USA. ; 1] Sansom Institute for Health Research, University of South Australia, Adelaide 5000, South Australia, Australia. [2] School of Population Health, University of South Australia, Adelaide 5000, South Australia, Australia. [3] South Australian Health and Medical Research Institute, Adelaide, South Australia 5000, Australia. [4] Population, Policy, and Practice, University College London Institute of Child Health, London WC1N 1EH, UK. ; 1] Research Unit of Molecular Epidemiology, Helmholtz Zentrum Munchen - German Research Center for Environmental Health, D-85764 Neuherberg, Germany. [2] Hannover Unified Biobank, Hannover Medical School, Hannover, D-30625 Hannover, Germany. ; 1] Department of Epidemiology and Biostatistics, Imperial College London, London W2 1PG, UK. [2] National Institute for Health and Welfare, FI-90101 Oulu, Finland. [3] MRC Health Protection Agency (HPA) Centre for Environment and Health, School of Public Health, Imperial College London, London W2 1PG, UK. [4] Unit of Primary Care, Oulu University Hospital, FI-90220 Oulu, Finland. [5] Institute of Health Sciences, University of Oulu, FI-90014 Oulu, Finland. [6] Institute of Health Sciences, University of Oulu, FI-90014 Oulu, Finland. ; 1] Department of Cardiology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. [2] Durrer Center for Cardiogenetic Research, Interuniversity Cardiology Institute Netherlands (ICIN), 3501 DG Utrecht, The Netherlands. [3] Interuniversity Cardiology Institute of the Netherlands (ICIN), 3501 DG Utrecht, The Netherlands. ; 1] National Institute for Health and Welfare, FI-00271 Helsinki, Finland. [2] Institute for Molecular Medicine, University of Helsinki, FI-00014 Helsinki, Finland. [3] Hjelt Institute Department of Public Health, University of Helsinki, FI-00014 Helsinki, Finland. ; 1] Institute of Health Sciences, University of Oulu, FI-90014 Oulu, Finland. [2] Unit of Primary Health Care/General Practice, Oulu University Hospital, FI-90220 Oulu, Finland. ; 1] Department for Health Evidence, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands. [2] Department of Urology, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands. ; 1] Ealing Hospital NHS Trust, Middlesex UB1 3HW, UK. [2] National Heart and Lung Institute, Imperial College London, London SW3 6LY, UK. [3] Imperial College Healthcare NHS Trust, London W12 0HS, UK. ; 1] Department of Epidemiology and Public Health, University College London, London WC1E 6BT, UK. [2] Department of Biological and Social Epidemiology, University of Essex, Wivenhoe Park, Colchester, Essex CO4 3SQ, UK. ; Department of Medicine, Kuopio University Hospital and University of Eastern Finland, FI-70210 Kuopio, Finland. ; 1] Kuopio Research Institute of Exercise Medicine, 70100 Kuopio, Finland. [2] Department of Physiology, Institute of Biomedicine, University of Eastern Finland, Kuopio Campus, FI-70211 Kuopio, Finland. [3] Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital and University of Eastern Finland, FI-70210 Kuopio, Finland. ; 1] MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK. [2] Department of Epidemiology and Public Health, University College London, London WC1E 6BT, UK. ; Department of Clinical Chemistry, Fimlab Laboratories and School of Medicine University of Tampere, FI-33520 Tampere, Finland. ; 1] Steno Diabetes Center A/S, Gentofte DK-2820, Denmark. [2] Lund University Diabetes Centre and Department of Clinical Science, Diabetes &Endocrinology Unit, Lund University, Malmo 221 00, Sweden. ; 1] Institut Universitaire de Cardiologie et de Pneumologie de Quebec, Faculty of Medicine, Laval University, Quebec, QC G1V 0A6, Canada. [2] Institute of Nutrition and Functional Foods, Laval University, Quebec, QC G1V 0A6, Canada. ; Department of Genetics, Rutgers University, Piscataway, New Jersey 08854, USA. ; Department of Biostatistics, University of Washington, Seattle, Washington 98195, USA. ; Department of Surgery, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands. ; 1] Estonian Genome Center, University of Tartu, Tartu 51010, Estonia. [2] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. [3] Department of Biostatistics, University of Liverpool, Liverpool L69 3GA, UK. ; Department of Pediatrics, University of Iowa, Iowa City, Iowa 52242, USA. ; 1] MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK. [2] MRC Unit for Lifelong Health and Ageing at University College London, London WC1B 5JU, UK. ; Illumina, Inc, Little Chesterford, Cambridge CB10 1XL, UK. ; 1] Research Unit of Molecular Epidemiology, Helmholtz Zentrum Munchen - German Research Center for Environmental Health, D-85764 Neuherberg, Germany. [2] Deutsches Forschungszentrum fur Herz-Kreislauferkrankungen (DZHK) (German Research Centre for Cardiovascular Research), Munich Heart Alliance, D-80636 Munich, Germany. [3] Institute of Epidemiology II, Helmholtz Zentrum Munchen - German Research Center for Environmental Health, Neuherberg, Germany, D-85764 Neuherberg, Germany. ; University of Groningen, University Medical Center Groningen, Department of Pulmonary Medicine and Tuberculosis, Groningen, The Netherlands. ; 1] Center for Biomedicine, European Academy Bozen, Bolzano (EURAC), Bolzano 39100, Italy (affiliated institute of the University of Lubeck, D-23562 Lubeck, Germany). [2] Department of Neurology, General Central Hospital, Bolzano 39100, Italy. ; 1] Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. [2] Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts 02115, USA. ; 1] Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, FI-20521 Turku, Finland. [2] Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, FI-20521 Turku, Finland. ; Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana 70808, USA. ; 1] Department of Genetics, Washington University School of Medicine, St Louis, Missouri 63110, USA. [2] Division of Biostatistics, Washington University School of Medicine, St Louis, Missouri 63110, USA. [3] Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri 63110, USA. ; 1] Division of Biostatistics, Washington University School of Medicine, St Louis, Missouri 63110, USA. [2] Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri 63110, USA. ; 1] Montreal Heart Institute, Montreal, Quebec H1T 1C8, Canada. [2] Universite de Montreal, Montreal, Quebec H1T 1C8, Canada. ; Center for Systems Genomics, The Pennsylvania State University, University Park, Pennsylvania 16802, USA. ; 1] Centre for Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG, UK. [2] Croatian Centre for Global Health, Faculty of Medicine, University of Split, 21000 Split, Croatia. ; South Carelia Central Hospital, 53130 Lappeenranta, Finland. ; 1] Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universitat Dresden, D-01307 Dresden, Germany. [2] Paul Langerhans Institute Dresden, German Center for Diabetes Research (DZD), 01307 Dresden, Germany. ; International Centre for Circulatory Health, Imperial College London, London W2 1PG, UK. ; 1] Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. [2] Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. [3] Geriatric Research and Education Clinical Center, Vetrans Administration Medical Center, Baltimore, Maryland 21201, USA. ; Helsinki University Central Hospital Heart and Lung Center, Department of Medicine, Helsinki University Central Hospital, FI-00290 Helsinki, Finland. ; 1] Institute of Genetic Epidemiology, Helmholtz Zentrum Munchen - German Research Center for Environmental Health, D-85764 Neuherberg, Germany. [2] Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-Universitat, D-81377 Munich, Germany. ; 1] Sorbonne Universites, UPMC Univ Paris 06, UMR S 1166, F-75013 Paris, France. [2] INSERM, UMR S 1166, Team Genomics and Physiopathology of Cardiovascular Diseases, F-75013 Paris, France. [3] Institute for Cardiometabolism And Nutrition (ICAN), F-75013 Paris, France. ; Department of Kinesiology, Laval University, Quebec QC G1V 0A6, Canada. ; Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita di Milano &Centro Cardiologico Monzino, Instituto di Ricovero e Cura a Carattere Scientifico, Milan 20133, Italy. ; 1] Institute of Nutrition and Functional Foods, Laval University, Quebec, QC G1V 0A6, Canada. [2] Department of Food Science and Nutrition, Laval University, Quebec QC G1V 0A6, Canada. ; 1] Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, D-17475 Greifswald, Germany. [2] DZHK (Deutsches Zentrum fur Herz-Kreislaufforschung - German Centre for Cardiovascular Research), partner site Greifswald, D-17475 Greifswald, Germany. ; Department of Internal Medicine, University Hospital (CHUV) and University of Lausanne, Lausanne 1011, Switzerland. ; Department of Epidemiology, Erasmus MC University Medical Center, 3015GE Rotterdam, The Netherlands. ; Department of Nutrition, University of North Carolina, Chapel Hill, North Carolina 27599, USA. ; Institut Pasteur de Lille; INSERM, U744; Universite de Lille 2; F-59000 Lille, France. ; 1] Institute of Cardiovascular Science, University College London, London WC1E 6BT, UK. [2] Durrer Center for Cardiogenetic Research, Interuniversity Cardiology Institute Netherlands (ICIN), 3501 DG Utrecht, The Netherlands. [3] Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands. ; Department of Medicine, Stanford University School of Medicine, Palo Alto, California 94304, USA. ; 1] Lee Kong Chian School of Medicine, Imperial College London and Nanyang Technological University, Singapore, 637553 Singapore, Singapore. [2] Department of Internal Medicine I, Ulm University Medical Centre, D-89081 Ulm, Germany. ; Health Science Center at Houston, University of Texas, Houston, Texas 77030, USA. ; 1] Ealing Hospital NHS Trust, Middlesex UB1 3HW, UK. [2] Department of Epidemiology and Biostatistics, Imperial College London, London W2 1PG, UK. [3] Imperial College Healthcare NHS Trust, London W12 0HS, UK. ; 1] Department of Medical Genetics, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands. [2] Department of Medicine, Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. [3] Department of Epidemiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands. ; 1] Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts 02115, USA. [2] Department of Clinical Sciences, Genetic &Molecular Epidemiology Unit, Lund University Diabetes Center, Skane University Hosptial, Malmo 205 02, Sweden. [3] Department of Public Health and Clinical Medicine, Unit of Medicine, Umea University, Umea 901 87, Sweden. ; 1] Department of Genomics of Common Disease, School of Public Health, Imperial College London, Hammersmith Hospital, London W12 0NN, UK. [2] CNRS UMR 8199, F-59019 Lille, France. [3] European Genomic Institute for Diabetes, F-59000 Lille, France. [4] Universite de Lille 2, F-59000 Lille, France. ; 1] Institute for Molecular Medicine, University of Helsinki, FI-00014 Helsinki, Finland. [2] Lund University Diabetes Centre and Department of Clinical Science, Diabetes &Endocrinology Unit, Lund University, Malmo 221 00, Sweden. ; 1] PathWest Laboratory Medicine of Western Australia, Nedlands, Western Australia 6009, Australia. [2] Pathology and Laboratory Medicine, The University of Western Australia, Perth, Western Australia 6009, Australia. [3] School of Population Health, The University of Western Australia, Nedlands, Western Australia 6009, Australia. ; 1] Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. [2] Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts 02115, USA. [3] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA. ; Albert Einstein College of Medicine, Department of Epidemiology and Population Health, Belfer 1306, New York 10461, USA. ; Department of Epidemiology and Public Health, University College London, London WC1E 6BT, UK. ; Center for Human Genetics, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157, USA. ; 1] Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty of Mannheim, University of Heidelberg, D-68187 Mannheim, Germany. [2] Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz 8036, Austria. [3] Synlab Academy, Synlab Services GmbH, 68163 Mannheim, Germany. ; 1] Department of Medicine, Stanford University School of Medicine, Palo Alto, California 94304, USA. [2] Department of Clinical Medicine, Copenhagen University, 2200 Copenhagen, Denmark. ; 1] Genetic Epidemiology Unit, Department of Epidemiology, Erasmus MC University Medical Center, 3015 GE Rotterdam, The Netherlands. [2] Center for Medical Sytems Biology, 2300 RC Leiden, The Netherlands. [3] Department of Clinical Genetics, Erasmus MC University Medical Center, 3000 CA Rotterdam, The Netherlands. ; 1] Estonian Genome Center, University of Tartu, Tartu 51010, Estonia. [2] National Institute for Health and Welfare, FI-00271 Helsinki, Finland. [3] Institute for Molecular Medicine, University of Helsinki, FI-00014 Helsinki, Finland. ; 1] Institute of Nutrition and Functional Foods, Laval University, Quebec, QC G1V 0A6, Canada. [2] Department of Kinesiology, Laval University, Quebec QC G1V 0A6, Canada. ; Population, Policy, and Practice, University College London Institute of Child Health, London WC1N 1EH, UK. ; 1] Kuopio Research Institute of Exercise Medicine, 70100 Kuopio, Finland. [2] Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital and University of Eastern Finland, FI-70210 Kuopio, Finland. ; 1] Finnish Diabetes Association, Kirjoniementie 15, FI-33680 Tampere, Finland. [2] Pirkanmaa Hospital District, FI-33521 Tampere, Finland. ; 1] Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK. [2] Center for Non-Communicable Diseases, Karatchi, Pakistan. [3] Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. ; BHF Glasgow Cardiovascular Research Centre, Division of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow G12 8TA, UK. ; Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York 10580, USA. ; 1] deCODE Genetics, Amgen Inc., Reykjavik 101, Iceland. [2] Faculty of Medicine, University of Iceland, Reykjavik 101, Iceland. ; 1] National Institute for Health and Welfare, FI-00271 Helsinki, Finland. [2] Institute for Health Research, University Hospital of La Paz (IdiPaz), 28046 Madrid, Spain. [3] Diabetes Research Group, King Abdulaziz University, 21589 Jeddah, Saudi Arabia. [4] Centre for Vascular Prevention, Danube-University Krems, 3500 Krems, Austria. ; 1] Department of Public Health and Clinical Nutrition, University of Eastern Finland, Finland. [2] Research Unit, Kuopio University Hospital, FI-70210 Kuopio, Finland. ; 1] Department of Genetics, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands. [2] Department of Cardiology, University Medical Center Groningen, University of Groningen, 9700RB Groningen, The Netherlands. [3] Durrer Center for Cardiogenetic Research, Interuniversity Cardiology Institute Netherlands (ICIN), 3501 DG Utrecht, The Netherlands. ; Institute of Cellular Medicine, Newcastle University, Newcastle NE1 7RU, UK. ; 1] DZHK (Deutsches Zentrum fur Herz-Kreislaufforschung - German Centre for Cardiovascular Research), partner site Greifswald, D-17475 Greifswald, Germany. [2] Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, D-17475 Greifswald, Germany. ; 1] Institute of Medical Informatics, Biometry and Epidemiology, Chair of Epidemiology, Ludwig-Maximilians-Universitat, D-85764 Munich, Germany. [2] Klinikum Grosshadern, D-81377 Munich, Germany. [3] Institute of Epidemiology I, Helmholtz Zentrum Munchen - German Research Center for Environmental Health, Neuherberg, Germany, D-85764 Neuherberg, Germany. ; Department of Pulmonology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands. ; 1] Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK. [2] William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK. [3] Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, 21589 Jeddah, Saudi Arabia. ; National Heart, Lung, and Blood Institute, the Framingham Heart Study, Framingham, Massachusetts 01702, USA. ; 1] Department of Genetic Epidemiology, Institute of Epidemiology and Preventive Medicine, University of Regensburg, D-93053 Regensburg, Germany. [2] Institute of Genetic Epidemiology, Helmholtz Zentrum Munchen - German Research Center for Environmental Health, D-85764 Neuherberg, Germany. ; 1] Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. [2] Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. ; Division of Population Health Sciences &Education, St George's, University of London, London SW17 0RE, UK. ; 1] Genetic Epidemiology Unit, Department of Epidemiology, Erasmus MC University Medical Center, 3015 GE Rotterdam, The Netherlands. [2] Netherlands Consortium for Healthy Aging (NCHA), 3015GE Rotterdam, The Netherlands. [3] Department of Epidemiology, Erasmus MC University Medical Center, 3015GE Rotterdam, The Netherlands. [4] Center for Medical Sytems Biology, 2300 RC Leiden, The Netherlands. ; 1] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. [2] Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford OX3 7LJ, UK. [3] Oxford NIHR Biomedical Research Centre, Oxford University Hospitals NHS Trust, Oxford OX3 7LJ, UK. ; 1] Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), University Hospital Essen, 45147 Essen, Germany. [2] Clinical Epidemiology, Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC), Jena University Hospital, 07743 Jena, Germany. ; 1] Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA. [2] Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 48109, USA. [3] Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109, USA. ; 1] Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA. [2] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. ; 1] Swiss Institute of Bioinformatics, Lausanne 1015, Switzerland. [2] Department of Medical Genetics, University of Lausanne, Lausanne 1005, Switzerland. [3] Service of Medical Genetics, CHUV University Hospital, 1011 Lausanne, Switzerland. ; 1] Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK. [2] University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 OQQ, UK. [3] NIHR Cambridge Biomedical Research Centre, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 OQQ, UK. ; 1] Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA. [2] Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA. ; 1] MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK. [2] The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA. [3] The Genetics of Obesity and Related Metabolic Traits Program, The Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA. [4] The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25673413" target="_blank"〉PubMed〈/a〉
    Keywords: Adipogenesis/genetics ; Adiposity/genetics ; Age Factors ; *Body Mass Index ; Continental Population Groups/genetics ; Energy Metabolism/genetics ; Europe/ethnology ; Female ; Genetic Predisposition to Disease/genetics ; *Genome-Wide Association Study ; Glutamic Acid/metabolism ; Humans ; Insulin/metabolism/secretion ; Male ; Obesity/*genetics/*metabolism ; Polymorphism, Single Nucleotide/genetics ; Quantitative Trait Loci/genetics ; Synapses/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 7
    Publication Date: 2015-04-04
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4544703/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4544703/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉van der Lee, Sven J -- Holstege, Henne -- Wong, Tsz Hang -- Jakobsdottir, Johanna -- Bis, Joshua C -- Chouraki, Vincent -- van Rooij, Jeroen G J -- Grove, Megan L -- Smith, Albert V -- Amin, Najaf -- Choi, Seung-Hoan -- Beiser, Alexa S -- Garcia, Melissa E -- van IJcken, Wilfred F J -- Pijnenburg, Yolande A L -- Louwersheimer, Eva -- Brouwer, Rutger W W -- van den Hout, Mirjam C G N -- Oole, Edwin -- Eirkisdottir, Gudny -- Levy, Daniel -- Rotter, Jerome I -- Emilsson, Valur -- O'Donnell, Christopher J -- Aspelund, Thor -- Uitterlinden, Andre G -- Launer, Lenore J -- Hofman, Albert -- Boerwinkle, Eric -- Psaty, Bruce M -- DeStefano, Anita L -- Scheltens, Philip -- Seshadri, Sudha -- van Swieten, John C -- Gudnason, Vilmundur -- van der Flier, Wiesje M -- Ikram, M Arfan -- van Duijn, Cornelia M -- R01 HL105756/HL/NHLBI NIH HHS/ -- UL1 TR000124/TR/NCATS NIH HHS/ -- England -- Nature. 2015 Apr 2;520(7545):E2-3. doi: 10.1038/nature14038.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Epidemiology, Erasmus Medical Center, Rotterdam 3000 CA, The Netherlands. ; 1] Alzheimer Center, Department of Neurology, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam 1081 HZ, The Netherlands [2] Department of Clinical Genetics, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam 1081 HZ, The Netherlands. ; Department of Neurology, Erasmus Medical Center, Rotterdam 3000 CA, The Netherlands. ; Icelandic Heart Association, Kopavogur 201, Iceland. ; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington 98101, USA. ; 1] National Heart, Lung and Blood Institute Framingham Heart Study, Framingham, Massachusetts 01702-5827, USA [2] Boston University School of Medicine, Boston, Massachusetts 02118, USA. ; Department of Internal Medicine, Erasmus Medical Center, Rotterdam 3000 CA, The Netherlands. ; School of Public Health, Human Genetics Center, University of Texas Health Science Center at Houston, Houston, Texas 77030, USA. ; 1] Icelandic Heart Association, Kopavogur 201, Iceland [2] Faculty of Medicine, University of Iceland, Reykjavik 101, Iceland. ; 1] National Heart, Lung and Blood Institute Framingham Heart Study, Framingham, Massachusetts 01702-5827, USA [2] Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts 02118, USA. ; Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, Maryland 20892, USA. ; Center for Biomics, Erasmus Medical Center, Rotterdam 3000 CA, The Netherlands. ; Alzheimer Center, Department of Neurology, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam 1081 HZ, The Netherlands. ; 1] National Heart, Lung and Blood Institute Framingham Heart Study, Framingham, Massachusetts 01702-5827, USA [2] Boston University School of Medicine, Boston, Massachusetts 02118, USA [3] National Heart, Lung, and Blood Institute, Intramural Research Program, National Institutes of Health, Bethesda, Maryland 20892, USA. ; Institute for Translational Genomics and Population Sciences, Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center, Torrance, California 90502, USA. ; 1] Icelandic Heart Association, Kopavogur 201, Iceland [2] Faculty of Pharmaceutical Sciences, University of Iceland, Reykjavik 101, Iceland. ; 1] National Heart, Lung and Blood Institute Framingham Heart Study, Framingham, Massachusetts 01702-5827, USA [2] National Heart, Lung, and Blood Institute, Intramural Research Program, National Institutes of Health, Bethesda, Maryland 20892, USA. ; 1] Icelandic Heart Association, Kopavogur 201, Iceland [2] Centre for Public Health, University of Iceland, Reykjavik 101, Iceland. ; 1] Department of Epidemiology, Erasmus Medical Center, Rotterdam 3000 CA, The Netherlands [2] Department of Internal Medicine, Erasmus Medical Center, Rotterdam 3000 CA, The Netherlands [3] Netherlands Consortium on Health Aging and National Genomics Initiative, Leiden 2300 RC, The Netherlands. ; 1] School of Public Health, Human Genetics Center, University of Texas Health Science Center at Houston, Houston, Texas 77030, USA [2] Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA. ; 1] Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington 98101, USA [2] Department of Epidemiology, University of Washington, Seattle, Washington 98101, USA [3] Group Health Research Institute, Seattle, Washington 98101-1448, USA. ; 1] Alzheimer Center, Department of Neurology, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam 1081 HZ, The Netherlands [2] Department of Neurology, Erasmus Medical Center, Rotterdam 3000 CA, The Netherlands. ; 1] Alzheimer Center, Department of Neurology, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam 1081 HZ, The Netherlands [2] Department of Epidemiology &Biostatistics, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam 1081 HZ, The Netherlands. ; 1] Department of Epidemiology, Erasmus Medical Center, Rotterdam 3000 CA, The Netherlands [2] Department of Neurology, Erasmus Medical Center, Rotterdam 3000 CA, The Netherlands [3] Departments of Radiology, Erasmus Medical Center, Rotterdam 3000 CA, The Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25832410" target="_blank"〉PubMed〈/a〉
    Keywords: Alzheimer Disease/*genetics ; Female ; Genetic Predisposition to Disease/*genetics ; Genetic Variation/*genetics ; Humans ; Male ; Phospholipase D/*genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 8
    Publication Date: 2013-04-09
    Description: Cancers acquire resistance to systemic treatment as a result of clonal evolution and selection. Repeat biopsies to study genomic evolution as a result of therapy are difficult, invasive and may be confounded by intra-tumour heterogeneity. Recent studies have shown that genomic alterations in solid cancers can be characterized by massively parallel sequencing of circulating cell-free tumour DNA released from cancer cells into plasma, representing a non-invasive liquid biopsy. Here we report sequencing of cancer exomes in serial plasma samples to track genomic evolution of metastatic cancers in response to therapy. Six patients with advanced breast, ovarian and lung cancers were followed over 1-2 years. For each case, exome sequencing was performed on 2-5 plasma samples (19 in total) spanning multiple courses of treatment, at selected time points when the allele fraction of tumour mutations in plasma was high, allowing improved sensitivity. For two cases, synchronous biopsies were also analysed, confirming genome-wide representation of the tumour genome in plasma. Quantification of allele fractions in plasma identified increased representation of mutant alleles in association with emergence of therapy resistance. These included an activating mutation in PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha) following treatment with paclitaxel; a truncating mutation in RB1 (retinoblastoma 1) following treatment with cisplatin; a truncating mutation in MED1 (mediator complex subunit 1) following treatment with tamoxifen and trastuzumab, and following subsequent treatment with lapatinib, a splicing mutation in GAS6 (growth arrest-specific 6) in the same patient; and a resistance-conferring mutation in EGFR (epidermal growth factor receptor; T790M) following treatment with gefitinib. These results establish proof of principle that exome-wide analysis of circulating tumour DNA could complement current invasive biopsy approaches to identify mutations associated with acquired drug resistance in advanced cancers. Serial analysis of cancer genomes in plasma constitutes a new paradigm for the study of clonal evolution in human cancers.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Murtaza, Muhammed -- Dawson, Sarah-Jane -- Tsui, Dana W Y -- Gale, Davina -- Forshew, Tim -- Piskorz, Anna M -- Parkinson, Christine -- Chin, Suet-Feung -- Kingsbury, Zoya -- Wong, Alvin S C -- Marass, Francesco -- Humphray, Sean -- Hadfield, James -- Bentley, David -- Chin, Tan Min -- Brenton, James D -- Caldas, Carlos -- Rosenfeld, Nitzan -- Cancer Research UK/United Kingdom -- England -- Nature. 2013 May 2;497(7447):108-12. doi: 10.1038/nature12065. Epub 2013 Apr 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Research UK Cambridge Institute and University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23563269" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Antineoplastic Agents/pharmacology/*therapeutic use ; Breast Neoplasms/drug therapy/genetics/pathology ; Carcinoma, Non-Small-Cell Lung/drug therapy/genetics/pathology ; DNA Mutational Analysis ; DNA, Neoplasm/*analysis/*genetics ; Drug Resistance, Neoplasm/drug effects/*genetics ; Evolution, Molecular ; Exome/genetics ; Female ; Genome, Human/genetics ; Genomics ; Humans ; Intercellular Signaling Peptides and Proteins/genetics ; Lung Neoplasms/drug therapy/genetics/pathology ; Mediator Complex Subunit 1/genetics ; Neoplasms/*drug therapy/*genetics/pathology ; Ovarian Neoplasms/drug therapy/genetics/pathology ; Phosphatidylinositol 3-Kinases/genetics ; Plasma/*chemistry ; Receptor, Epidermal Growth Factor/genetics ; Retinoblastoma Protein/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 9
    Publication Date: 2014-08-30
    Description: Without an approved vaccine or treatments, Ebola outbreak management has been limited to palliative care and barrier methods to prevent transmission. These approaches, however, have yet to end the 2014 outbreak of Ebola after its prolonged presence in West Africa. Here we show that a combination of monoclonal antibodies (ZMapp), optimized from two previous antibody cocktails, is able to rescue 100% of rhesus macaques when treatment is initiated up to 5 days post-challenge. High fever, viraemia and abnormalities in blood count and blood chemistry were evident in many animals before ZMapp intervention. Advanced disease, as indicated by elevated liver enzymes, mucosal haemorrhages and generalized petechia could be reversed, leading to full recovery. ELISA and neutralizing antibody assays indicate that ZMapp is cross-reactive with the Guinean variant of Ebola. ZMapp exceeds the efficacy of any other therapeutics described so far, and results warrant further development of this cocktail for clinical use.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4214273/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4214273/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Qiu, Xiangguo -- Wong, Gary -- Audet, Jonathan -- Bello, Alexander -- Fernando, Lisa -- Alimonti, Judie B -- Fausther-Bovendo, Hugues -- Wei, Haiyan -- Aviles, Jenna -- Hiatt, Ernie -- Johnson, Ashley -- Morton, Josh -- Swope, Kelsi -- Bohorov, Ognian -- Bohorova, Natasha -- Goodman, Charles -- Kim, Do -- Pauly, Michael H -- Velasco, Jesus -- Pettitt, James -- Olinger, Gene G -- Whaley, Kevin -- Xu, Bianli -- Strong, James E -- Zeitlin, Larry -- Kobinger, Gary P -- U19 AI109762/AI/NIAID NIH HHS/ -- U19AI109762/AI/NIAID NIH HHS/ -- Canadian Institutes of Health Research/Canada -- England -- Nature. 2014 Oct 2;514(7520):47-53. doi: 10.1038/nature13777. Epub 2014 Aug 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Laboratory for Zoonotic Diseases and Special Pathogens, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada. ; 1] National Laboratory for Zoonotic Diseases and Special Pathogens, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada [2] Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba R3E 0J9, Canada. ; 1] National Laboratory for Zoonotic Diseases and Special Pathogens, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada [2] Institute of Infectious Disease, Henan Centre for Disease Control and Prevention, Zhengzhou, 450012 Henan, China. ; Kentucky BioProcessing, Owensboro, Kentucky 42301, USA. ; Mapp Biopharmaceutical Inc., San Diego, California 92121, USA. ; 1] United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, Maryland 21702, USA [2] Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland 21702, USA. ; Institute of Infectious Disease, Henan Centre for Disease Control and Prevention, Zhengzhou, 450012 Henan, China. ; 1] National Laboratory for Zoonotic Diseases and Special Pathogens, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada [2] Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba R3E 0J9, Canada [3] Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba R3A 1S1, Canada. ; 1] National Laboratory for Zoonotic Diseases and Special Pathogens, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada [2] Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba R3E 0J9, Canada [3] Department of Immunology, University of Manitoba, Winnipeg, Manitoba R3E 0T5, Canada [4] Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25171469" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Antibodies, Monoclonal/immunology/*therapeutic use ; Antibodies, Neutralizing/immunology/therapeutic use ; Antibodies, Viral/immunology/*therapeutic use ; Cross Reactions/immunology ; Ebolavirus/immunology ; Enzyme-Linked Immunosorbent Assay ; Female ; Guinea ; Guinea Pigs ; Hemorrhagic Fever, Ebola/blood/*drug therapy/immunology/virology ; *Immunization, Passive ; Macaca mulatta/immunology/virology ; Male ; Molecular Sequence Data ; Sequence Alignment ; Viral Envelope Proteins/chemistry/immunology ; Viremia/drug therapy/immunology/virology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 10
    Publication Date: 2014-05-16
    Description: Docosahexaenoic acid (DHA) is an omega-3 fatty acid that is essential for normal brain growth and cognitive function. Consistent with its importance in the brain, DHA is highly enriched in brain phospholipids. Despite being an abundant fatty acid in brain phospholipids, DHA cannot be de novo synthesized in brain and must be imported across the blood-brain barrier, but mechanisms for DHA uptake in brain have remained enigmatic. Here we identify a member of the major facilitator superfamily--Mfsd2a (previously an orphan transporter)--as the major transporter for DHA uptake into brain. Mfsd2a is found to be expressed exclusively in endothelium of the blood-brain barrier of micro-vessels. Lipidomic analysis indicates that Mfsd2a-deficient (Mfsd2a-knockout) mice show markedly reduced levels of DHA in brain accompanied by neuronal cell loss in hippocampus and cerebellum, as well as cognitive deficits and severe anxiety, and microcephaly. Unexpectedly, cell-based studies indicate that Mfsd2a transports DHA in the form of lysophosphatidylcholine (LPC), but not unesterified fatty acid, in a sodium-dependent manner. Notably, Mfsd2a transports common plasma LPCs carrying long-chain fatty acids such LPC oleate and LPC palmitate, but not LPCs with less than a 14-carbon acyl chain. Moreover, we determine that the phosphor-zwitterionic headgroup of LPC is critical for transport. Importantly, Mfsd2a-knockout mice have markedly reduced uptake of labelled LPC DHA, and other LPCs, from plasma into brain, demonstrating that Mfsd2a is required for brain uptake of DHA. Our findings reveal an unexpected essential physiological role of plasma-derived LPCs in brain growth and function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nguyen, Long N -- Ma, Dongliang -- Shui, Guanghou -- Wong, Peiyan -- Cazenave-Gassiot, Amaury -- Zhang, Xiaodong -- Wenk, Markus R -- Goh, Eyleen L K -- Silver, David L -- England -- Nature. 2014 May 22;509(7501):503-6. doi: 10.1038/nature13241. Epub 2014 May 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Signature Research Program in Cardiovascular and Metabolic Disorders, Duke-NUS Graduate Medical School Singapore, 8 College Road, 169857 Singapore. ; Signature Research Program in Neuroscience and Behavioral Disorders, Duke-NUS Graduate Medical School Singapore, 8 College Road, 169857 Singapore. ; Department of Biochemistry, National University of Singapore, 8 Medical Drive, Block MD7, 117597 Singapore.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24828044" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anxiety/physiopathology ; Biological Transport ; Blood-Brain Barrier/metabolism ; Brain/*metabolism/pathology/physiopathology ; Cognition Disorders/pathology/physiopathology ; Docosahexaenoic Acids/deficiency/*metabolism ; Endothelium, Vascular/metabolism ; Female ; Lysophosphatidylcholines/chemistry/metabolism ; Male ; Membrane Transport Proteins/deficiency/genetics/*metabolism ; Mice ; Mice, Knockout ; Microcephaly/metabolism/pathology ; Microvessels/metabolism ; Neurons/metabolism/pathology ; Organ Size ; Sodium/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...