Characterization of genetic loci that affect susceptibility to inflammatory bowel diseases in African Americans.

摘要: Background & Aims Inflammatory bowel disease (IBD) has familial aggregation in African Americans (AAs), but little is known about the molecular genetic susceptibility. Mapping studies using Immunochip genotyping array expand number of susceptibility loci for IBD Caucasians to 163, contribution 163 and European admixture risk AAs unclear. We performed a mapping study determine whether also affect identify new associated loci. Methods recruited with without (controls) from 34 centers United States; additional controls were collected 4 other studies. Association mapped 1088 patients Crohn's disease, 361 ulcerative colitis, 62 type unknown, 1797 controls; 130,241 autosomal single-nucleotide polymorphisms (SNPs) analyzed. Results The strongest associations observed between colitis HLA rs9271366 ( P  = 7.5 × 10 −6 ), 5p13.1 rs4286721 3.5 KAT2A rs730086 2.3 ). Additional suggestive −5 ) African-specific SNPs STAT5A STAT3 ; IL23R , IL12B C2orf43; near HDAC11 LINC00994 . latter 3 have not been previously IBD, require replication. Established Caucasian replicated −4 at NOD2 5p15 IKZF3 Significant was 17q12−17q21.31 IZKF3 through 10q11.23−10q21.2, 15q22.2–15q23, 16p12.2−16p12.1. Network analyses showed significant enrichment (false discovery rate genes that encode members JAK−STAT, cytokine, chemokine signaling pathways, as well those involved pathogenesis measles. Conclusions In analysis 3308 AA cases controls, we found many variants association evidence these diseases AAs; IBD. complex factors or protection against different populations further study.