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  • 1
    Publication Date: 2012-11-07
    Description: Crohn's disease and ulcerative colitis, the two common forms of inflammatory bowel disease (IBD), affect over 2.5 million people of European ancestry, with rising prevalence in other populations. Genome-wide association studies and subsequent meta-analyses of these two diseases as separate phenotypes have implicated previously unsuspected mechanisms, such as autophagy, in their pathogenesis and showed that some IBD loci are shared with other inflammatory diseases. Here we expand on the knowledge of relevant pathways by undertaking a meta-analysis of Crohn's disease and ulcerative colitis genome-wide association scans, followed by extensive validation of significant findings, with a combined total of more than 75,000 cases and controls. We identify 71 new associations, for a total of 163 IBD loci, that meet genome-wide significance thresholds. Most loci contribute to both phenotypes, and both directional (consistently favouring one allele over the course of human history) and balancing (favouring the retention of both alleles within populations) selection effects are evident. Many IBD loci are also implicated in other immune-mediated disorders, most notably with ankylosing spondylitis and psoriasis. We also observe considerable overlap between susceptibility loci for IBD and mycobacterial infection. Gene co-expression network analysis emphasizes this relationship, with pathways shared between host responses to mycobacteria and those predisposing to IBD.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3491803/" 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/PMC3491803/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jostins, Luke -- Ripke, Stephan -- Weersma, Rinse K -- Duerr, Richard H -- McGovern, Dermot P -- Hui, Ken Y -- Lee, James C -- Schumm, L Philip -- Sharma, Yashoda -- Anderson, Carl A -- Essers, Jonah -- Mitrovic, Mitja -- Ning, Kaida -- Cleynen, Isabelle -- Theatre, Emilie -- Spain, Sarah L -- Raychaudhuri, Soumya -- Goyette, Philippe -- Wei, Zhi -- Abraham, Clara -- Achkar, Jean-Paul -- Ahmad, Tariq -- Amininejad, Leila -- Ananthakrishnan, Ashwin N -- Andersen, Vibeke -- Andrews, Jane M -- Baidoo, Leonard -- Balschun, Tobias -- Bampton, Peter A -- Bitton, Alain -- Boucher, Gabrielle -- Brand, Stephan -- Buning, Carsten -- Cohain, Ariella -- Cichon, Sven -- D'Amato, Mauro -- De Jong, Dirk -- Devaney, Kathy L -- Dubinsky, Marla -- Edwards, Cathryn -- Ellinghaus, David -- Ferguson, Lynnette R -- Franchimont, Denis -- Fransen, Karin -- Gearry, Richard -- Georges, Michel -- Gieger, Christian -- Glas, Jurgen -- Haritunians, Talin -- Hart, Ailsa -- Hawkey, Chris -- Hedl, Matija -- Hu, Xinli -- Karlsen, Tom H -- Kupcinskas, Limas -- Kugathasan, Subra -- Latiano, Anna -- Laukens, Debby -- Lawrance, Ian C -- Lees, Charlie W -- Louis, Edouard -- Mahy, Gillian -- Mansfield, John -- Morgan, Angharad R -- Mowat, Craig -- Newman, William -- Palmieri, Orazio -- Ponsioen, Cyriel Y -- Potocnik, Uros -- Prescott, Natalie J -- Regueiro, Miguel -- Rotter, Jerome I -- Russell, Richard K -- Sanderson, Jeremy D -- Sans, Miquel -- Satsangi, Jack -- Schreiber, Stefan -- Simms, Lisa A -- Sventoraityte, Jurgita -- Targan, Stephan R -- Taylor, Kent D -- Tremelling, Mark -- Verspaget, Hein W -- De Vos, Martine -- Wijmenga, Cisca -- Wilson, David C -- Winkelmann, Juliane -- Xavier, Ramnik J -- Zeissig, Sebastian -- Zhang, Bin -- Zhang, Clarence K -- Zhao, Hongyu -- International IBD Genetics Consortium (IIBDGC) -- Silverberg, Mark S -- Annese, Vito -- Hakonarson, Hakon -- Brant, Steven R -- Radford-Smith, Graham -- Mathew, Christopher G -- Rioux, John D -- Schadt, Eric E -- Daly, Mark J -- Franke, Andre -- Parkes, Miles -- Vermeire, Severine -- Barrett, Jeffrey C -- Cho, Judy H -- 068545/Z/02/Wellcome Trust/United Kingdom -- 083948/Z/07/Z/Wellcome Trust/United Kingdom -- 085475/B/08/Z/Wellcome Trust/United Kingdom -- 085475/Z/08/Z/Wellcome Trust/United Kingdom -- 089120/Wellcome Trust/United Kingdom -- 090532/Wellcome Trust/United Kingdom -- 098051/Wellcome Trust/United Kingdom -- AI062773/AI/NIAID NIH HHS/ -- CA141743/CA/NCI NIH HHS/ -- CZB/4/540/Chief Scientist Office/United Kingdom -- DK043351/DK/NIDDK NIH HHS/ -- DK062413/DK/NIDDK NIH HHS/ -- DK062420/DK/NIDDK NIH HHS/ -- DK062422/DK/NIDDK NIH HHS/ -- DK062423/DK/NIDDK NIH HHS/ -- DK062429/DK/NIDDK NIH HHS/ -- DK062429-S1/DK/NIDDK NIH HHS/ -- DK062431/DK/NIDDK NIH HHS/ -- DK062432/DK/NIDDK NIH HHS/ -- DK063491/DK/NIDDK NIH HHS/ -- DK076984/DK/NIDDK NIH HHS/ -- DK084554/DK/NIDDK NIH HHS/ -- DK83756/DK/NIDDK NIH HHS/ -- ETM/137/Chief Scientist Office/United Kingdom -- ETM/75/Chief Scientist Office/United Kingdom -- G0000934/British Heart Foundation/United Kingdom -- G0600329/Medical Research Council/United Kingdom -- G0800675/Medical Research Council/United Kingdom -- G0800759/Medical Research Council/United Kingdom -- G1002033/Medical Research Council/United Kingdom -- K23 DK097142/DK/NIDDK NIH HHS/ -- M01-RR00425/RR/NCRR NIH HHS/ -- P01 DK046763/DK/NIDDK NIH HHS/ -- P01DK046763/DK/NIDDK NIH HHS/ -- P30 DK043351/DK/NIDDK NIH HHS/ -- R01 CA141743/CA/NCI NIH HHS/ -- R01 DK055731/DK/NIDDK NIH HHS/ -- T32 GM007205/GM/NIGMS NIH HHS/ -- T32GM07205/GM/NIGMS NIH HHS/ -- U01 DK062418/DK/NIDDK NIH HHS/ -- U01 DK062420/DK/NIDDK NIH HHS/ -- U01 DK062422/DK/NIDDK NIH HHS/ -- U01 DK062429/DK/NIDDK NIH HHS/ -- U01 DK062431/DK/NIDDK NIH HHS/ -- U01 DK062432/DK/NIDDK NIH HHS/ -- UL1 TR000005/TR/NCATS NIH HHS/ -- UL1 TR000124/TR/NCATS NIH HHS/ -- UL1 TR000124-01/TR/NCATS NIH HHS/ -- Medical Research Council/United Kingdom -- England -- Nature. 2012 Nov 1;491(7422):119-24. doi: 10.1038/nature11582.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1HH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23128233" target="_blank"〉PubMed〈/a〉
    Keywords: Colitis, Ulcerative/genetics/immunology/microbiology/physiopathology ; Crohn Disease/genetics/immunology/microbiology/physiopathology ; Genetic Predisposition to Disease/*genetics ; Genome, Human/genetics ; *Genome-Wide Association Study ; Haplotypes/genetics ; *Host-Pathogen Interactions/genetics/immunology ; Humans ; Inflammatory Bowel Diseases/*genetics/immunology/*microbiology/physiopathology ; Mycobacterium/*immunology/pathogenicity ; Mycobacterium Infections/genetics/microbiology ; Mycobacterium tuberculosis/immunology/pathogenicity ; Phenotype ; Polymorphism, Single Nucleotide/genetics ; Reproducibility of Results
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  GMDS 2012; 57. Jahrestagung der Deutschen Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie e.V. (GMDS); 20120916-20120920; Braunschweig; DOC12gmds169 /20120913/
    Publication Date: 2012-09-14
    Keywords: decision-analytic model ; prostate cancer ; PSA-screening ; review ; ddc: 610
    Language: English
    Type: conferenceObject
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  • 3
    ISSN: 1432-0630
    Keywords: 61.10 ; 61.50
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract The growth rates of small (length 〈1 mm) crystals of Rochelle salt grown with and without a magnetic field have been measured at constant supersaturation (4%). It has been shown that some crystals grown in the presence of a magnetic field exhibit a decrease in the linear growth rate in the [010] direction relative to that shown under normal conditions. It was further noticed that a few crystals of the total number showed slight increases in growth rate. The fact that a majority of crystals showed a decrease in growth rate has given rise to speculations that this should be caused by an increase of strain (mosaic spread), resulting from a change of the mode of incorporation of the growth units into the crystal surface brought about by the applied magnetic field. The results show that most of crystals grown in the magnetic field have a higher mosaic spread and lower growth rate than observed during growth without an applied field. An increase in growth rate in the presence of the magnetic field, observed for a few crystals, might be explained by the relaxation of this strain by formation of dislocations, which in turn enhance the growth rate.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1420-9071
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Halogenated benzenesulfonanilides have potent fasciolicidal activity. The efficacy of 1 such compound in mice, sheep, and cattle is reported.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1420-9071
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Zusammenfassung Die Wirkung von vier faszioliziden Agentien (Rafoxanid, Oxyklozanid, Nitroxynil und Diamphenethid) wurde im Mäuseversuch verglichen. Alle vier Substanzen waren gegen unreifeFasciola hepatica wirksam und entfalteten ihre höchste Wirksamkeit gegen spätere unreife Stadien, mit Ausnahme von Diamphenethid, welches gegen die Frühstadien der unreifen Parasiten am stärksten war.
    Type of Medium: Electronic Resource
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  • 6
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1520-4804
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1573-0972
    Keywords: Alcohol ; beer ; dialysis ; membrane-filtration ; transmembrane pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract An 8-μm thick Cuprophane hollow-fibre membrane not only had a higher ultrafiltration coefficient than an 11-μm thick membrane but was more permeable and selective for ethanol dialysis and extract removal from beer. Transmembrane pressures above 40 Pa did not affect alcohol removal but did prevent further extract removal and therefore improved the final beer quality. To achieve selective removal of alcohol, beer flow rates must be above the critical velocities but remain below values which would require too great a membrane area.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1572-8838
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Electrical Engineering, Measurement and Control Technology
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1573-6784
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Summary Using experimental results of chemical composition of initial beer, dialysed beer and dialysate, obtained in laboratory scale equipment for dialysis, basic parameters for mass transfer kinetics were determined. It was found that absolute pressure in the system under the medium flow rate of 300 ml/min increased alcohol separate selectivity. As the result of the specific two-phase character of beer, the working pressure in the system for beer dialysis did not fall below 3–4 bar.
    Type of Medium: Electronic Resource
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