Dataset Information

The AVPR1A gene and substance use disorders: association, replication, and functional evidence.

ABSTRACT:

Background

The liability to addiction has been shown to be highly genetically correlated across drug classes, suggesting nondrug-specific mechanisms.

Methods

In 757 subjects, we performed association analysis between 1536 single nucleotide polymorphisms (SNPs) in 106 candidate genes and a drug use disorder diagnosis (DUD).

Results

Associations (p ≤ .0008) were detected with three SNPs in the arginine vasopressin 1A receptor gene, AVPR1A, with a gene-wise p value of 3 × 10(-5). Bioinformatic evidence points to a role for rs11174811 (microRNA binding site disruption) in AVPR1A function. Based on literature implicating AVPR1A in social bonding, we tested spousal satisfaction as a mediator of the association of rs11174811 with the DUD. Spousal satisfaction was significantly associated with DUD in males (p < .0001). The functional AVPR1A SNP, rs11174811, was associated with spousal satisfaction in males (p = .007). Spousal satisfaction was a significant mediator of the relationship between rs11174811 and DUD. We also present replication of the association in males between rs11174811 and substance use in one clinically ascertained (n = 1399) and one epidemiologic sample (n = 2231). The direction of the association is consistent across the clinically-ascertained samples but reversed in the epidemiologic sample. Lastly, we found a significant impact of rs11174811 genotype on AVPR1A expression in a postmortem brain sample.

Conclusions

The findings of this study call for expansion of research into the role of the arginine vasopressin and other neuropeptide system variation in DUD liability.

SUBMITTER: Maher BS

PROVIDER: S-EPMC4083653 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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Publications

The AVPR1A gene and substance use disorders: association, replication, and functional evidence.

Maher Brion S BS Vladimirov Vladimir I VI Latendresse Shawn J SJ Thiselton Dawn L DL McNamee Rebecca R Kang Moonsu M Bigdeli Tim B TB Chen Xiangning X Riley Brien P BP Hettema John M JM Chilcoat Howard H Heidbreder Christian C Muglia Pierandrea P Murrelle E Lenn EL Dick Danielle M DM Aliev Fazil F Agrawal Arpana A Edenberg Howard J HJ Kramer John J Nurnberger John J Tischfield Jay A JA Devlin Bernie B Ferrell Robert E RE Kirillova Galina P GP Tarter Ralph E RE Kendler Kenneth S KS Vanyukov Michael M MM

Biological psychiatry 20110422 6

<h4>Background</h4>The liability to addiction has been shown to be highly genetically correlated across drug classes, suggesting nondrug-specific mechanisms.<h4>Methods</h4>In 757 subjects, we performed association analysis between 1536 single nucleotide polymorphisms (SNPs) in 106 candidate genes and a drug use disorder diagnosis (DUD).<h4>Results</h4>Associations (p ≤ .0008) were detected with three SNPs in the arginine vasopressin 1A receptor gene, AVPR1A, with a gene-wise p value of 3 × 10(- ...[more]

PMID: 21514569

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Dataset Information

The AVPR1A gene and substance use disorders: association, replication, and functional evidence.

Background

Methods

Results

Conclusions

Publications

The AVPR1A gene and substance use disorders: association, replication, and functional evidence.

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