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. 2012 Dec;18(12):2277-87.
doi: 10.1002/ibd.22931. Epub 2012 Mar 12.

Contribution of higher risk genes and European admixture to Crohn's disease in African Americans

Ming-Hsi Wang  1 , Toshihiko Okazaki, Subra Kugathasan, Judy H Cho, Kim L Isaacs, James D Lewis, Duane T Smoot, John F Valentine, Howard A Kader, Jean G Ford, Mary L Harris, Maria Oliva-Hemker, Carmen Cuffari, Michael S Torbenson, Richard H Duerr, Mark S Silverberg, John D Rioux, Kent D Taylor, Geoffrey C Nguyen, Yuqiong Wu, Lisa W Datta, Stanley Hooker, Themistocles Dassopoulos, Rick A Kittles, Linda W H Kao, Steven R Brant
Affiliations

Contribution of higher risk genes and European admixture to Crohn's disease in African Americans

Ming-Hsi Wang et al. Inflamm Bowel Dis. 2012 Dec.

Abstract

Background: African Americans (AAs) are an admixed population of West African (WA) and European ancestry (EA). Crohn's disease (CD) susceptibility genes have not been established. We therefore evaluated the contribution of European admixture and major established risk genes to AA CD.

Methods: Ninety-seven admixture informative markers were genotyped for ancestry estimates using STRUCTURE. Overall, 354 AA CD cases and 354 ethnicity-matched controls were genotyped for total 21 single nucleotide polymorphisms (SNPs) in ATG16L1, NOD2, IBD5, IL23R and IRGM by TaqMan or direct sequencing. Association was evaluated by logistic regression, adjusted for ancestry.

Results: Mean EA was similar among the CD cases and controls (20.9% and 20.4%, respectively, P = 0.58). No significant admixture differences were observed among 211 to 227 cases stratified by phenotypic subclassifications including onset, surgery, site, and behavior. CD was associated with NOD2 carrier (6.93% CD, 2.15% Controls, P = 0.007), ATG16L1 Thr300Ala (36.1% CD, 29.3% Controls, P = 0.003), SLC22A4 and SLC22A5 (IBD5 locus) functional SNPs (Leu503Phe [10.5% CD, 7.6% Controls, P = 0.05] and g-207c [41.3% CD, 35.7% Controls, P = 0.03], respectively), and IL23R rs2201841 (18.2% CD, 13.8% Controls, P = 0.03), but not IRGM variants, nor three African ancestral NOD2 nonsynonymous variants. IBD5 risk was recessive. An all-minor allele IBD5 haplotype from EA was associated (P = 0.05), whereas a more common haplotype isolating g-207c was not.

Conclusions: Specific functional gene variations contribute significantly to AA CD risk. Established NOD2, SLC22A4-A5, and ATG16L1 variants show increased CD risk, with IBD5 recessive. Although CD is more common in whites, European admixture is similar among AA cases and controls.

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Conflict of interest statement

Disclosures for all authors: No relevant potential conflicts

Figures

Figure 1
Figure 1
Cumulative proportion of persons with increment of West African ancestry for (a) CD (solid) vs. controls (dashed); (b)complicated (B2 or B3) (solid) vs. inflammatory behavior (dashed); and (c) ileal (L1 or L3) (solid) vs. colon-only (L2) disease (dashed) sites. Linear regression analyses treating WA as a continuous trait observed a borderline difference in complicated vs. inflammatory behavior (p=0.07), and no differences in CD vs. controls (p=0.57) or ileal vs. colon-only sites (p=0.55).
Figure 1
Figure 1
Cumulative proportion of persons with increment of West African ancestry for (a) CD (solid) vs. controls (dashed); (b)complicated (B2 or B3) (solid) vs. inflammatory behavior (dashed); and (c) ileal (L1 or L3) (solid) vs. colon-only (L2) disease (dashed) sites. Linear regression analyses treating WA as a continuous trait observed a borderline difference in complicated vs. inflammatory behavior (p=0.07), and no differences in CD vs. controls (p=0.57) or ileal vs. colon-only sites (p=0.55).
Figure 1
Figure 1
Cumulative proportion of persons with increment of West African ancestry for (a) CD (solid) vs. controls (dashed); (b)complicated (B2 or B3) (solid) vs. inflammatory behavior (dashed); and (c) ileal (L1 or L3) (solid) vs. colon-only (L2) disease (dashed) sites. Linear regression analyses treating WA as a continuous trait observed a borderline difference in complicated vs. inflammatory behavior (p=0.07), and no differences in CD vs. controls (p=0.57) or ileal vs. colon-only sites (p=0.55).
See this image and copyright information in PMC

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