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 [IBD-U]) and 5002 individuals without IBD (controls,
identified from the Health Retirement Study and Kaiser Permanente database).
Single-nucleotide polymorphisms (SNPs) associated at P<5.0×10−8 in
meta-analysis with a nominal evidence (P<.05) in each scan were considered to have
genome-wide significance.
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 associations 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<1.6×10−6): ADCY3, CXCR6, HLA-DRB1 to HLA-DQA1 (genome-wide
significance on conditioning), IL12B, PTGER4, and TNC for IBD; IL23R, PTGER4, and SNX20
(in strong linkage disequilibrium with NOD2) for CD; and KCNQ2 (near TNFRSF6B) for UC.
Several of these genes, such as TNC (near TNFSF15), CXCR6, and genes associated with IBD
at the HLA locus, contained SNPs with unique association patterns with African-specific
alleles.
Conclusions
We performed a genome-wide association study of African Americans with IBD and
identified loci associated with CD and UC in only this population; we also replicated
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.