Genome-Wide Association Study Identifies African-Specific Susceptibility Loci in African Americans With Inflammatory Bowel Disease
Brant SR, Okou DT, Simpson CL, Cutler DJ, Haritunians T, Bradfield JP, Chopra P, Prince J, Begum F, Kumar A, Huang C, Venkateswaran S, Datta LW, Wei Z, Thomas K, Herrinton LJ, Klapproth JA, Quiros AJ, Seminerio J, Liu Z, Alexander JS, Baldassano RN, Dudley-Brown S, Cross RK, Dassopoulos T, Denson LA, Dhere TA, Dryden GW, Hanson JS, Hou JK, Hussain SZ, Hyams JS, Isaacs KL, Kader H, Kappelman MD, Katz J, Kellermayer R, Kirschner BS, Kuemmerle JF, Kwon JH, Lazarev M, Li E, Mack D, Mannon P, Moulton DE, Newberry RD, Osuntokun BO, Patel AS, Saeed SA, Targan SR, Valentine JF, Wang MH, Zonca M, Rioux JD, Duerr RH, Silverberg MS, Cho JH, Hakonarson H, Zwick ME, McGovern DP, Kugathasan S. Genome-Wide Association Study Identifies African-Specific Susceptibility Loci in African Americans With Inflammatory Bowel Disease. Gastroenterology. 2017 Jan;152(1):206-217.e2.
BACKGROUND & AIMS: The inflammatory bowel diseases (IBD) ulcerative colitis (UC) and Crohn's disease (CD) cause significant morbidity and are increasing in prevalence among all populations, including African Americans. More than 200 susceptibility loci have been identified in populations of predominantly European ancestry, but few loci have been associated with IBD in other ethnicities.
METHODS: We performed 2 high-density, genome-wide scans comprising 2345 cases of African Americans with IBD (1646 with CD, 583 with UC, and 116 inflammatory bowel disease unclassified) and 5002 individuals without IBD (controls, identified from the Health Retirement Study and Kaiser Permanente database). Single-nucleotide polymorphisms (SNPs) associated at P < 5.0 × 10
RESULTS: We detected SNPs at HLA-DRB1, and African-specific SNPs at ZNF649 and LSAMP, with associations of genome-wide significance for UC. We detected SNPs at USP25 with associations of genome-wide significance for IBD. No associations of genome-wide significance were detected for CD. In addition, 9 genes previously associated with IBD contained SNPs with significant evidence for replication (P < 1.6 × 10
CONCLUSIONS: We performed a genome-wide association study of African Americans with IBD and identified loci associated with UC in only this population; we also replicated IBD, CD, and UC loci identified in European populations. The detection of variants associated with IBD risk in only people of African descent demonstrates the importance of studying the genetics of IBD and other complex diseases in populations beyond those of European ancestry.
Medical Subject Headings
Adenylyl Cyclases; African Americans; Case-Control Studies; Cell Adhesion Molecules, Neuronal; Colitis, Ulcerative; Crohn Disease; European Continental Ancestry Group; GPI-Linked Proteins; Genetic Predisposition to Disease; Genome-Wide Association Study; Genotyping Techniques; HLA-DQ alpha-Chains; HLA-DRB1 Chains; Humans; Interleukin-12 Subunit p40; KCNQ2 Potassium Channel; Polymorphism, Single Nucleotide; Receptors, CXCR6; Receptors, Chemokine; Receptors, Interleukin; Receptors, Prostaglandin E, EP4 Subtype; Receptors, Virus; Repressor Proteins; Sorting Nexins; Tenascin; Ubiquitin Thiolesterase