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