Variation in NGFB is associated with primary affective disorders in women

Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA.
American Journal of Medical Genetics Part B Neuropsychiatric Genetics (Impact Factor: 3.42). 06/2011; 156B(4):401-12. DOI: 10.1002/ajmg.b.31175
Source: PubMed


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.

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    • "This non-synonymous SNP produces an alanine to valine substitution at amino acid position 35 and is thought to have a possible functional role on intracellular processing and secretion of NGF[118]. Allelic variation at this locus has shown associations with anxiety-related traits and affective disorders [119,120]. "
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    • "In psychiatric research areas, Cui et al. (2011) reported that variation in NGF is associated with primary affective disorders in women. They investigated genetic variation in the NGF in 182 patients with primary affective disorders and 472 screened controls. "
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