Institute of Clinical Molecular Biology, Christian-Albrechts-University Kiel, Kiel, Germany.
Nat Genet. 2010 Dec;42(12):1118-25. doi: 10.1038/ng.717.
We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 × 10⁻⁸). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease.
我们对六项克罗恩病全基因组关联研究(GWAS)进行了荟萃分析,共纳入 6333 名受影响个体(病例)和 15056 名对照,并对 15694 例病例、14026 名对照和 414 对父母-子女三胞胎中的最高关联信号进行了随访。我们确定了 30 个新的易感性位点,达到全基因组显著水平(P < 5 × 10⁻⁸)。一系列的计算分析突出了这些位点内的特定基因,并与人工整理一起,暗示了具有功能意义的候选基因,包括 SMAD3、ERAP2、IL10、IL2RA、TYK2、FUT2、DNMT3A、DENND1B、BACH2 和 TAGAP。结合以前确认的位点,这些结果确定了 71 个不同的位点,这些位点与克罗恩病的全基因组显著关联具有全基因组显著证据。