{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:13:04Z","timestamp":1787008384018,"version":"build-2736575974"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2024,1,17]],"date-time":"2024-01-17T00:00:00Z","timestamp":1705449600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Peter Boris Chair in Addictions Research and a Canada Research Chair in Translational Addiction Research","award":["CRC-2020-00170"],"award-info":[{"award-number":["CRC-2020-00170"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,1,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>This study uses a high-resolution phenome-wide approach to evaluate the motivational mechanisms of polygenic risk scores (PRSs) that have been robustly associated with coarse alcohol phenotypes in large-scale studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In a community-based sample of 1534 Europeans, we examined genome-wide PRSs for the Alcohol Use Disorders Identification Test (AUDIT), drinks per week, alcohol use disorder (AUD), problematic alcohol use (PAU), and general addiction, in relation to 42 curated phenotypes. The curated phenotypes were in seven categories: alcohol consumption, alcohol reinforcing value, drinking motives, other addictive behaviors, commonly comorbid psychiatric syndromes, impulsivity, and personality traits.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The PRS for each alcohol phenotype was validated via its within-sample association with the corresponding phenotype (adjusted R2s\u2009=\u20090.35\u20131.68%, Ps\u2009=\u20090.012\u20133.6\u2009\u00d7\u200910\u22127) with the exception of AUD. All PRSs were positively associated with alcohol reinforcing value and drinking motives, with the strongest effects from AUDIT-consumption (adjusted R2s\u2009=\u20090.45\u20131.33%, Ps\u2009=\u20090.006\u20133.6\u2009\u00d7\u200910\u22125) and drinks per week PRSs (adjusted R2s\u2009=\u20090.52\u20132.28%, Ps\u2009=\u20090.004\u20136.6\u2009\u00d7\u200910\u22129). Furthermore, the PAU and drinks per week PRSs were positively associated with adverse childhood experiences (adjusted R2s\u2009=\u20090.6\u20130.7%, Ps\u2009=\u20090.0001\u20134.8\u2009\u00d7\u200910\u22124).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These results implicate alcohol reinforcing value and drinking motives as genetically-influenced mechanisms using PRSs for the first time. The findings also highlight the value of dissecting genetic influence on alcohol involvement through diverse phenotypic risk pathways but also the need for future studies with both phenotypic richness and larger samples.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/alcalc\/agad093","type":"journal-article","created":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T12:53:21Z","timestamp":1703163201000},"source":"Crossref","is-referenced-by-count":3,"title":["A high-resolution PheWAS approach to alcohol-related polygenic risk scores reveals mechanistic influences of alcohol reinforcing value and drinking motives"],"prefix":"10.1093","volume":"59","author":[{"given":"Wei Q","family":"Deng","sequence":"first","affiliation":[{"name":"Peter Boris Centre for Addictions Research, St. Joseph\u2019s Healthcare Hamilton , Hamilton, Ontario L8N 3K7 , Canada"},{"name":"Department of Psychiatry and Behavioural Neurosciences, McMaster University , Hamilton, Ontario L8N 3K7 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyla","family":"Belisario","sequence":"additional","affiliation":[{"name":"Peter Boris Centre for Addictions Research, St. Joseph\u2019s Healthcare Hamilton , Hamilton, Ontario L8N 3K7 , Canada"},{"name":"Department of Psychiatry and Behavioural Neurosciences, McMaster University , Hamilton, Ontario L8N 3K7 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua C","family":"Gray","sequence":"additional","affiliation":[{"name":"Department of Medical and Clinical Psychology, Uniformed Services University , Bethesda, MD 20814 , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily E","family":"Levitt","sequence":"additional","affiliation":[{"name":"Peter Boris Centre for Addictions Research, St. Joseph\u2019s Healthcare Hamilton , Hamilton, Ontario L8N 3K7 , Canada"},{"name":"Department of Psychiatry and Behavioural Neurosciences, McMaster University , Hamilton, Ontario L8N 3K7 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"MacKillop","sequence":"additional","affiliation":[{"name":"Peter Boris Centre for Addictions Research, St. Joseph\u2019s Healthcare Hamilton , Hamilton, Ontario L8N 3K7 , Canada"},{"name":"Department of Psychiatry and Behavioural Neurosciences, McMaster University , Hamilton, Ontario L8N 3K7 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,1,22]]},"reference":[{"key":"2024012314220649600_ref1","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.drugalcdep.2010.02.017","article-title":"An improved brief measure of cannabis misuse: the Cannabis Use Disorders Identification Test-Revised (CUDIT-R)","volume":"110","author":"Adamson","year":"2010","journal-title":"Drug Alcohol Depend"},{"key":"2024012314220649600_ref2","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.jsat.2006.10.001","article-title":"The self-report Drug Use Disorders Identification Test-Extended (DUDIT-E): reliability, validity, and motivational index","volume":"32","author":"Berman","year":"2007","journal-title":"J Subst Abuse Treat"},{"key":"2024012314220649600_ref5","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1016\/j.drugalcdep.2013.04.016","article-title":"Comorbidity of posttraumatic stress disorder with alcohol dependence among US adults: results from national epidemiological survey on alcohol and related conditions","volume":"132","author":"Blanco","year":"2013","journal-title":"Drug Alcohol Depend"},{"key":"2024012314220649600_ref7","volume-title":"Alcohol and health in Canada: a summary of evidence and guidelines for low-risk drinking","author":"Butt","year":"2011"},{"key":"2024012314220649600_ref8","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1080\/10550887.2019.1643211","article-title":"Addictive behaviors in alcohol use disorder: dysregulation of reward processing systems and maladaptive coping strategies","volume":"37","author":"Cavicchioli","year":"2018","journal-title":"J Addict Dis"},{"key":"2024012314220649600_ref9","doi-asserted-by":"crossref","DOI":"10.1016\/j.psychres.2020.113563","article-title":"Association between polymorphism in gene related to the dopamine circuit and motivations for drinking in patients with alcohol use disorder","volume":"295","author":"C\u00e9spedes","year":"2021","journal-title":"Psychiatry Res"},{"key":"2024012314220649600_ref11","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1038\/mp.2017.153","article-title":"Genome-wide association study of alcohol consumption and genetic overlap with other health-related traits in UK biobank (N=112117)","volume":"22","author":"Clarke","year":"2017","journal-title":"Mol Psychiatry"},{"key":"2024012314220649600_ref12","doi-asserted-by":"crossref","DOI":"10.1037\/0022-006X.53.2.189","article-title":"Social determinants of alcohol consumption. 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