title: Contribution of higher risk genes and European admixture to Crohn's disease in African Americans.
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.
authors.affiliation: Lyn P. and Harvey M. Meyerhoff Inflammatory Bowel Disease Center, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Ming-Hsi
authors.initials: MH
authors.lastname: Wang
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Okazaki
authors.forename: Subra
authors.initials: S
authors.lastname: Kugathasan
authors.forename: Judy H
authors.initials: JH
authors.lastname: Cho
authors.forename: Kim L
authors.initials: KL
authors.lastname: Isaacs
authors.forename: James D
authors.initials: JD
authors.lastname: Lewis
authors.forename: Duane T
authors.initials: DT
authors.lastname: Smoot
authors.forename: John F
authors.initials: JF
authors.lastname: Valentine
authors.forename: Howard A
authors.initials: HA
authors.lastname: Kader
authors.forename: Jean G
authors.initials: JG
authors.lastname: Ford
authors.forename: Mary L
authors.initials: ML
authors.lastname: Harris
authors.forename: Maria
authors.initials: M
authors.lastname: Oliva-Hemker
authors.forename: Carmen
authors.initials: C
authors.lastname: Cuffari
authors.forename: Michael S
authors.initials: MS
authors.lastname: Torbenson
authors.forename: Richard H
authors.initials: RH
authors.lastname: Duerr
authors.forename: Mark S
authors.initials: MS
authors.lastname: Silverberg
authors.forename: John D
authors.initials: JD
authors.lastname: Rioux
authors.forename: Kent D
authors.initials: KD
authors.lastname: Taylor
authors.forename: Geoffrey C
authors.initials: GC
authors.lastname: Nguyen
authors.forename: Yuqiong
authors.initials: Y
authors.lastname: Wu
authors.forename: Lisa W
authors.initials: LW
authors.lastname: Datta
authors.forename: Stanley
authors.initials: S
authors.lastname: Hooker
authors.forename: Themistocles
authors.initials: T
authors.lastname: Dassopoulos
authors.forename: Rick A
authors.initials: RA
authors.lastname: Kittles
authors.forename: Linda W H
authors.initials: LW
authors.lastname: Kao
authors.forename: Steven R
authors.initials: SR
authors.lastname: Brant
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins / Q000235:genetics; D003424:Crohn Disease / Q000235:genetics*; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics; D008297:Male; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018123:Receptors, Interleukin / Q000235:genetics; D012307:Risk Factors; D044465:White People / Q000235:genetics*
chemical_list: C518959:ATG16L1 protein, human; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; C515500:IL23R protein, human; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D018123:Receptors, Interleukin; D019204:GTP-Binding Proteins; C513539:IRGM protein, human