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

Biol Psychiatry. 2011 Sep 15;70(6):519-27. doi: 10.1016/j.biopsych.2011.02.023. Epub 2011 Apr 22.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Arginine Vasopressin / genetics*
  • Brain / metabolism
  • Case-Control Studies
  • Child
  • Female
  • Genetic Association Studies / statistics & numerical data*
  • Humans
  • Male
  • Object Attachment*
  • Polymorphism, Single Nucleotide / genetics
  • Receptors, Vasopressin / biosynthesis
  • Receptors, Vasopressin / genetics*
  • Sex Characteristics
  • Spouses / psychology*
  • Substance-Related Disorders / genetics*
  • Substance-Related Disorders / psychology
  • Twins / genetics
  • Twins / psychology


  • Receptors, Vasopressin
  • Arginine Vasopressin