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

Authors

  • Oloruntosin Adeyanju,

    1. Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia
    2. Children's Health Care of Atlanta, Atlanta, Georgia
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  • David T. Okou PhD,

    1. Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia
    2. Children's Health Care of Atlanta, Atlanta, Georgia
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  • Clifton Huang MD,

    1. Children's Health Care of Atlanta, Atlanta, Georgia
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  • Archana Kumar,

    1. Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia
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  • Cary Sauer MD,

    1. Children's Health Care of Atlanta, Atlanta, Georgia
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  • Courtney Galloway,

    1. Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia
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  • Mahadev Prasad MHSA,

    1. Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia
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  • Jon Waters BS,

    1. Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia
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  • David J. Cutler PhD,

    1. Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia
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  • Michael E. Zwick PhD,

    1. Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia
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  • Tanvi Dhere MD,

    1. Division of Gastroenterology and Hepatology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia
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  • Subra Kugathasan MD

    Corresponding author
    1. Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia
    2. Children's Health Care of Atlanta, Atlanta, Georgia
    • Emory University School of Medicine, Division of Pediatric Gastroenterology, Emory Children's Center, 2015 Uppergate Dr., Rm. 248, Atlanta, GA 30322
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  • 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.

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. (Inflamm Bowel Dis 2012;)

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