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Variation in NGFB is associated with primary affective disorders in women
Author(s) -
Cui Donghong,
Zhang Huiping,
Yang BaoZhu,
Listman Jennifer B.,
Li Dawei,
Price Lawrence H.,
Carpenter Linda L.,
Tyrka Audrey R.,
Anton Raymond F.,
Kranzler Henry R.,
Gelernter Joel
Publication year - 2011
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.31175
Subject(s) - single nucleotide polymorphism , haplotype , comorbidity , etiology , medicine , genetics , biology , genotype , gene
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.