Variation in NGFB is associated with primary affective disorders in women

Authors

  • Donghong Cui,

    1. Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut
    2. Veterans Affairs Connecticut Healthcare Center, West Haven, Connecticut
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  • Huiping Zhang,

    1. Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut
    2. Veterans Affairs Connecticut Healthcare Center, West Haven, Connecticut
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  • Bao-Zhu Yang,

    1. Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut
    2. Veterans Affairs Connecticut Healthcare Center, West Haven, Connecticut
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  • Jennifer B. Listman,

    1. Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut
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  • Dawei Li,

    1. Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut
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  • Lawrence H. Price,

    1. Department of Psychiatry & Human Behavior, Brown University, Providence, Rhode Island
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  • Linda L. Carpenter,

    1. Department of Psychiatry & Human Behavior, Brown University, Providence, Rhode Island
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  • Audrey R. Tyrka,

    1. Department of Psychiatry & Human Behavior, Brown University, Providence, Rhode Island
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  • Raymond F. Anton,

    1. Department of Psychiatry & Behavioral Sciences, Medical University of South Carolina, Charleston, South Carolina
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  • Henry R. Kranzler,

    1. Departments of Psychiatry and Genetics and Developmental Biology, University of Connecticut School of Medicine, Farmington, Connecticut
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  • Joel Gelernter

    Corresponding author
    1. Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut
    2. Veterans Affairs Connecticut Healthcare Center, West Haven, Connecticut
    3. Department of Psychiatry & Behavioral Sciences, Medical University of South Carolina, Charleston, South Carolina
    4. Department of Genetics, Yale University School of Medicine, New Haven, Connecticut
    5. Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut
    • Departments of Psychiatry, Genetics, and Neurobiology, Yale University School of Medicine, VA CT 116A2, 950 Campbell Avenue, West Haven, CT 06516.
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  • Some of these data were presented at the 58th Annual Meeting of the American Society of Human Genetics, Philadelphia PA, November 11–15, 2008.

  • How to Cite this Article: Cui D, Zhang H, Yang B-Z, Listman JB, Li D, Price LH, Carpenter LL, Tyrka AR, Anton RF, Kranzler HR, Gelernter J. 2011. Variation in NGFB Is Associated With Primary Affective Disorders in Women. Am J Med Genet Part B 156:401–412.

Abstract

Affective disorders (AFDs) are highly comorbid with substance dependence (SD) and both are genetically influenced. However, the specific etiology of the comorbidity is not well understood. We genotyped an array of 1,350 single nucleotide polymorphisms (SNPs) in or near 130 genes in 868 European-Americans (EAs), including 182 individuals with primary AFDs (PAFDs), 214 with SD comorbid with AFD (CAFD), and 472 screened controls. NGFB, which encodes nerve growth factor β and was represented in the array by 15 SNPs, showed the strongest evidence of association, but only among women with PAFDs. Six of the SNPs showed nominally significant association with PAFDs in women (P's = 0.0007–0.01); three (rs2856813, rs4332358, and rs10776799) were empirically significant based on 1,000,000 permutations (P's = 0.008–0.015). Seven haplotypes were significantly associated with PAFDs in women (P's = 0.0014–0.01), of which six were significant based on empirical permutation analysis (minimal P = 0.0045). Four diplotypes were significantly associated with PAFDs in women (global P's = 0.001–0.01). The specific diplotype GG-TC, reconstructed from rs2856813 and rs6678788, showed the strongest evidence of association with PAFDs in women (OR = 4.07, P = 4.2E−05). No SNPs or haplotypes were associated with PAFDs in men or with CAFDs in either sex. We conclude that variation in NGFB is a risk factor for PAFDs in women, but not for CAFD. © 2011 Wiley-Liss, Inc.

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