Reference : Deep resequencing of GWAS loci identifies independent rare variants associated with i...
Scientific journals : Article
Human health sciences : Gastroenterology & hepatology
http://hdl.handle.net/2268/138705
Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease.
English
Rivas, Manuel A. [> >]
Beaudoin, Melissa [> >]
Gardet, Agnes [> >]
Stevens, Christine [> >]
Sharma, Yashoda [> >]
Zhang, Clarence K. [> >]
Boucher, Gabrielle [> >]
Ripke, Stephan [> >]
Ellinghaus, David [> >]
Burtt, Noel [> >]
Fennell, Tim [> >]
Kirby, Andrew [> >]
Latiano, Anna [> >]
Goyette, Philippe [> >]
Green, Todd [> >]
Halfvarson, Jonas [> >]
Haritunians, Talin [> >]
Korn, Joshua M. [> >]
Kuruvilla, Finny [> >]
Lagace, Caroline [> >]
Neale, Benjamin [> >]
Lo, Ken Sin [> >]
Schumm, Phil [> >]
Torkvist, Leif [> >]
Dubinsky, Marla C. [> >]
Brant, Steven R. [> >]
Silverberg, Mark S. [> >]
Duerr, Richard H. [> >]
Altshuler, David [> >]
Gabriel, Stacey [> >]
Lettre, Guillaume [> >]
Franke, Andre [> >]
D'Amato, Mauro [> >]
McGovern, Dermot P. B. [> >]
Cho, Judy H. [> >]
Rioux, John D. [> >]
Xavier, Ramnik J. [> >]
Daly, Mark J. [> >]
LOUIS, Edouard [Centre Hospitalier Universitaire de Liège - CHU > > Gastro-Entérologie-Hépatologie >]
2012
Nature Genetics
43
11
1066-73
Yes (verified by ORBi)
International
1061-4036
1546-1718
United States
[en] Case-Control Studies ; Cell Line ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Inflammatory Bowel Diseases/genetics ; Nod2 Signaling Adaptor Protein/genetics ; RNA Splicing ; Receptors, Interleukin/genetics ; Sequence Analysis, DNA
[en] 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 x 10(-16), odds ratio approximately 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.
http://hdl.handle.net/2268/138705

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