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DOI 10.1038/nature11582

Медицинская библиотека · Nature · 2012

Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.

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, Büning 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 Jürgen, 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

СтатьяМетаанализПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАПеревод пока не подготовлен

Аннотация

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.

Для цитирования: 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, Büning 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 Jürgen, 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. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.. Nature. 2012. DOI: 10.1038/nature11582.

Предметные рубрики MeSH

Colitis, UlcerativeCrohn DiseaseGenetic Predisposition to DiseaseGenome, HumanGenome-Wide Association StudyHaplotypesHost-Pathogen InteractionsHumansInflammatory Bowel DiseasesMycobacteriumMycobacterium InfectionsMycobacterium tuberculosisPhenotypePolymorphism, Single NucleotideReproducibility of Results
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