@article{0c5657cae2a14ce0af3cd4e2f3010065,
title = "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.",
keywords = "Addiction, alcoholism, gene systems, genetic association, social relationships, vasopressin",
author = "Maher, {Brion S.} and Vladimirov, {Vladimir I.} and Latendresse, {Shawn J.} and Thiselton, {Dawn L.} and Rebecca McNamee and Moonsu Kang and Bigdeli, {Tim B.} and Xiangning Chen and Riley, {Brien P.} and Hettema, {John M.} and Howard Chilcoat and Christian Heidbreder and Pierandrea Muglia and Murrelle, {E. Lenn} and Dick, {Danielle M.} and Fazil Aliev and Arpana Agrawal and Edenberg, {Howard J.} and John Kramer and John Nurnberger and Tischfield, {Jay A.} and Bernie Devlin and Ferrell, {Robert E.} and Kirillova, {Galina P.} and Tarter, {Ralph E.} and Kendler, {Kenneth S.} and Vanyukov, {Michael M.}",
note = "Funding Information: This study was supported by the National Institute on Drug Abuse (Grant P50DA005605 to RET; Grants R01DA011922 , R01DA019157 , and K02DA018701 to MMV). The Collaborative Study on the Genetics of Alcoholism (COGA) is supported by National Institutes of Health Grant U10AA08401 . GlaxoSmithKline partially funded genotyping costs in the Center for Education and Drug Abuse Research/Substance Abuse and the Dopamine System samples. Funding Information: The Collaborative Study on the Genetics of Alcoholism, Principal Investigators B. Porjesz, V. Hesselbrock, H. Edenburg, and L. Bierut, includes 10 different centers: University of Connecticut (V. Hesselbrock); Indiana University (H.J. Edenburg, J. Nurnberger Jr., T. Foroud); University of Iowa (S. Kuperman, J. Kramer); State University of New York Downstate (B. Porjesz); Washington University in St. Louis (L. Bierut, A. Goate, J. Rice, K. Bucholz); University of California at San Diego (M. Schuckit); Rutgers University (J. Tischfield); Southwest Foundation (L. Almasy), Howard University (R. Taylor); and Virginia Commonwealth University (D. Dick). Other COGA collaborators contributing to the genome-wide association studies data set include: L. Bauer (University of Connecticut); D. Koller, S. O'Connor, L. Wetherill, X. Xuei (Indiana University); Grace Chan (University of Iowa); N. Manz, M. Rangaswamy (State University of New York Downstate); A. Hinrichs, J. Rohrbaugh, J-C Wang (Washington University in St. Louis); A. Brooks (Rutgers University); and F. Aliev (Virginia Commonwealth University). A. Parsian and M. Reilly are the National Institute on Alcohol Abuse and Alcoholism Staff Collaborators. We continue to be inspired by our memories of Henri Begleiter and Theodore Reich, founding Principal Investigator and Co-Principal Investigator of COGA, and also owe a debt of gratitude to other past organizers of COGA, including Ting-Kai Li, currently a consultant with COGA, P. Michael Conneally, Raymond Crowe, and Wendy Reich, for their critical contributions. This national collaborative study is supported by National Institutes of Health Grant U10AA008401 from the National Institute on Alcohol Abuse and Alcoholism and the National Institute on Drug Abuse. ",
year = "2011",
month = sep,
day = "15",
doi = "10.1016/j.biopsych.2011.02.023",
language = "English (US)",
volume = "70",
pages = "519--527",
journal = "Biological psychiatry",
issn = "0006-3223",
publisher = "Elsevier USA",
number = "6",
}