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• W2097804771 abstract "Mark Daly, Manuel Rivas and colleagues used next-generation sequencing to study the coding exons of 56 genes from regions previously associated with Crohn's disease. Follow-up analyses in independent case-control series confirmed association of many newly discovered rare variants with disease risk. 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." @default.
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• W2097804771 date "2011-10-09" @default.
• W2097804771 modified "2023-10-18" @default.
• W2097804771 title "Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease" @default.
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• W2097804771 doi "https://doi.org/10.1038/ng.952" @default.
• W2097804771 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3378381" @default.
• W2097804771 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21983784" @default.
• W2097804771 hasPublicationYear "2011" @default.
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