Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2011-11

AUTHORS

Manuel A Rivas, Mélissa Beaudoin, Agnes Gardet, Christine Stevens, Yashoda Sharma, Clarence K Zhang, Gabrielle Boucher, Stephan Ripke, David Ellinghaus, Noel Burtt, Tim Fennell, Andrew Kirby, Anna Latiano, Philippe Goyette, Todd Green, Jonas Halfvarson, Talin Haritunians, Joshua M Korn, Finny Kuruvilla, Caroline Lagacé, Benjamin Neale, Ken Sin Lo, Phil Schumm, Leif Törkvist, Institute of Diabetes and Digestive Kidney Diseases Inflammatory Bowel Disease Genetics Consortium, Inflammatory Bowel Disease Genetics Consortium, International Inflammatory Bowel Disease Genetics Consortium, Marla C Dubinsky, Steven R Brant, Mark S Silverberg, Richard H Duerr, David Altshuler, Stacey Gabriel, Guillaume Lettre, Andre Franke, Mauro D'Amato, Dermot P B McGovern, Judy H Cho, John D Rioux, Ramnik J Xavier, Mark J Daly

ABSTRACT

More than 1,000 susceptibility loci have been identified through genome-wide association studies (GWAS) of common variants; however, the specific genes and full allelic spectrum of causal variants underlying these findings have not yet been defined. Here we used pooled next-generation sequencing to study 56 genes from regions associated with Crohn's disease in 350 cases and 350 controls. Through follow-up genotyping of 70 rare and low-frequency protein-altering variants in nine independent case-control series (16,054 Crohn's disease cases, 12,153 ulcerative colitis cases and 17,575 healthy controls), we identified four additional independent risk factors in NOD2, two additional protective variants in IL23R, a highly significant association with a protective splice variant in CARD9 (P < 1 × 10(-16), odds ratio ≈ 0.29) and additional associations with coding variants in IL18RAP, CUL2, C1orf106, PTPN22 and MUC19. We extend the results of successful GWAS by identifying new, rare and probably functional variants that could aid functional experiments and predictive models. More... »

PAGES

1066

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng.952

    DOI

    http://dx.doi.org/10.1038/ng.952

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1043485621

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/21983784


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