title: Common NOD2 risk variants in African Americans with Crohn's disease are due exclusively to recent Caucasian admixture.
abstract: BACKGROUND
  Crohn's disease (CD) is highly heritable. NOD2 has emerged as the main susceptibility gene among individuals of European ancestry; however, NOD2 does not appear to contribute to CD susceptibility among many non-European populations. Today's African American (AA) population represents an admixture of West African (80%) and European (20%) ancestry. Since genotype-based tools are becoming increasingly available for CD, it is important that we validate the risk variants in different populations, such as admixed AAs.
  
  
  METHODS
  We analyzed the NOD2 variants among admixed AAs (n = 321, 240 with CD and 111 healthy controls [HCs]) and nonadmixed West Africans (n = 40) by genotyping four known disease-causing NOD variants. We extracted the publicly available 1000 Genomes data on NOD2 variants from 500 subjects of West African origin. Association with disease was evaluated by logistic regression.
  
  
  RESULTS
  An association with CD was found for the classical single nucleotide polymorphism (SNP) 1007fs (2.6% CD, 0% HC, P = 0.012); there was no association when the genotypic and allelic frequencies of the risk alleles were compared for SNPs R702W and G908R. No known NOD2 risk alleles were seen in either the West African cohort or in subjects of African ancestry from the 1000 Genomes project.
  
  
  CONCLUSIONS
  The NOD2 gene is a risk for CD in AAs, although the allele frequencies and the attributable risk are much lower compared with Caucasians. The risk alleles are not seen in the West African population, suggesting that the risk for CD contributed by NOD2 among AAs is due exclusively to recent European admixture.
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
authors.forename: Oloruntosin
authors.initials: O
authors.lastname: Adeyanju
authors.forename: David T
authors.initials: DT
authors.lastname: Okou
authors.forename: Clifton
authors.initials: C
authors.lastname: Huang
authors.forename: Archana
authors.initials: A
authors.lastname: Kumar
authors.forename: Cary
authors.initials: C
authors.lastname: Sauer
authors.forename: Courtney
authors.initials: C
authors.lastname: Galloway
authors.forename: Mahadev
authors.initials: M
authors.lastname: Prasad
authors.forename: Jon
authors.initials: J
authors.lastname: Waters
authors.forename: David J
authors.initials: DJ
authors.lastname: Cutler
authors.forename: Michael E
authors.initials: ME
authors.lastname: Zwick
authors.forename: Tanvi
authors.initials: T
authors.lastname: Dhere
authors.forename: Subra
authors.initials: S
authors.lastname: Kugathasan
mesh_terms: D000354:Africa, Western; D001741:Black or African American / Q000235:genetics*; D000483:Alleles; D003424:Crohn Disease / Q000235:genetics*; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors; D044465:White People / Q000235:genetics*
chemical_list: C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein