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Author Notes:

Correspondence: Subra Kugathasan, MD, Emory University School of Medicine, Division of Pediatric Gastroenterology, Emory Children's Center, 2015 Uppergate Drive, room 248, Atlanta, GA 30322; Tel: 404 727 4542, Fax: 404 727 4069, Email: skugath@emory.edu

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Research Funding:

This work was supported by grants from the National Institutes of Health (DK087694) and in part by PHS Grants (UL1 RR025008, KL2 RR025009) from the Clinical and Translational Science Award program, NIH, National Center for Research Resources.

Keywords:

  • African Americans
  • Crohn’s disease
  • NOD2

The common NOD2 risk variants in African Americans with Crohn's disease are due exclusively to recent Caucasian admixture

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Journal Title:

Inflammatory Bowel Diseases

Volume:

Volume 18, Number 12

Publisher:

, Pages 2357-2359

Type of Work:

Article | Post-print: After Peer Review

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) and non-admixed West Africans (n=40) by genotyping for 4 known disease-causing NOD variants. We extracted the publically 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 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 to Caucasians. The risk alleles are not seen in the West African population suggesting the risk for CD contributed by NOD2 among AAs is due exclusively to recent European admixture

Copyright information:

© Crohn's & Colitis Foundation of America, Inc.

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