The AVPR1A gene and substance use disorders: association, replication, and functional evidence. Academic Article uri icon

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.

published proceedings

  • Biol Psychiatry

author list (cited authors)

  • Maher, B. S., Vladimirov, V. I., Latendresse, S. J., Thiselton, D. L., McNamee, R., Kang, M., ... Vanyukov, M. M.

complete list of authors

  • Maher, Brion S||Vladimirov, Vladimir I||Latendresse, Shawn J||Thiselton, Dawn L||McNamee, Rebecca||Kang, Moonsu||Bigdeli, Tim B||Chen, Xiangning||Riley, Brien P||Hettema, John M||Chilcoat, Howard||Heidbreder, Christian||Muglia, Pierandrea||Murrelle, E Lenn||Dick, Danielle M||Aliev, Fazil||Agrawal, Arpana||Edenberg, Howard J||Kramer, John||Nurnberger, John||Tischfield, Jay A||Devlin, Bernie||Ferrell, Robert E||Kirillova, Galina P||Tarter, Ralph E||Kendler, Kenneth S||Vanyukov, Michael M

publication date

  • January 1, 2011 11:11 AM