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dc.contributor.authorNurnberger, John I
dc.contributor.authorWang, Yumin
dc.contributor.authorZang, Yong
dc.contributor.authorLai, Dongbing
dc.contributor.authorWetherill, Leah
dc.contributor.authorEdenberg, Howard J
dc.contributor.authorAliev, Fazil
dc.contributor.authorPlawecki, Martin H
dc.contributor.authorChorlian, David
dc.contributor.authorChan, Grace
dc.contributor.authorBucholz, Kathleen
dc.contributor.authorBauer, Lance
dc.contributor.authorKamarajan, Chella
dc.contributor.authorSalvatore, Jessica E
dc.contributor.authorKapoor, Manav
dc.contributor.authorHesselbrock, Victor
dc.contributor.authorDick, Danielle
dc.contributor.authorBierut, Laura
dc.contributor.authorMcCutcheon, Vivia
dc.contributor.authorMeyers, Jacquelyn L
dc.contributor.authorPorjesz, Bernice
dc.contributor.authorKramer, John
dc.contributor.authorKuperman, Samuel
dc.contributor.authorKinreich, Sivan
dc.contributor.authorAnokhin, Andrey P
dc.identifier.citationNurnberger JI Jr, Wang Y, Zang Y, Lai D, Wetherill L, Edenberg HJ, Aliev F, Plawecki MH, Chorlian D, Chan G, Bucholz K, Bauer L, Kamarajan C, Salvatore JE, Kapoor M, Hesselbrock V, Dick D, Bierut L, McCutcheon V, Meyers JL, Porjesz B, Kramer J, Kuperman S, Kinreich S, Anokhin AP; Collaborative Study on the Genetics of Alcoholism. High Polygenic Risk Scores Are Associated With Early Age of Onset of Alcohol Use Disorder in Adolescents and Young Adults at Risk. Biol Psychiatry Glob Open Sci. 2021 Nov 1;2(4):379-388. doi: 10.1016/j.bpsgos.2021.10.007. PMID: 36324664; PMCID: PMC9616304.en_US
dc.description.abstractBackground: Genome-wide association studies have been conducted in alcohol use disorder (AUD), and they permit the use of polygenic risk scores (PRSs), in combination with clinical variables, to predict the onset of AUD in vulnerable populations. Methods: A total of 2794 adolescent/young adult subjects from the Collaborative Study on the Genetics of Alcoholism were followed, with clinical assessments every 2 years. Subjects were genotyped using a genome-wide chip. Separate PRS analyses were performed for subjects of European ancestry and African ancestry. Age of onset of DSM-5 AUD was evaluated using the Cox proportional hazard model. Predictive power was assessed using receiver operating characteristic curves and by analysis of the distribution of PRS. Results: European ancestry subjects with higher than median PRSs were at greater risk for onset of AUD than subjects with lower than median PRSs (p = 3 × 10-7). Area under the curve for the receiver operating characteristic analysis peaked at 0.88 to 0.95 using PRS plus sex, family history, comorbid disorders, age at first drink, and peer drinking; predictive power was primarily driven by clinical variables. In this high-risk sample, European ancestry subjects with a PRS score in the highest quartile showed a 72% risk for developing AUD and a 35% risk of developing severe AUD (compared with risks of 54% and 16%, respectively, in the lowest quartile). Conclusions: Predictive power for PRSs in the extremes of the distribution suggests that these may have future clinical utility. Uncertainties in interpretation at the individual level still preclude current application.en_US
dc.rights© 2021 The Authors.
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.subjectAlcohol use disorderen_US
dc.subjectClinical variablesen_US
dc.subjectPolygenic risk scoresen_US
dc.subjectPrediction of illnessen_US
dc.subjectReceiver operating characteristics curvesen_US
dc.subjectSurvival analysisen_US
dc.titleHigh Polygenic Risk Scores Are Associated With Early Age of Onset of Alcohol Use Disorder in Adolescents and Young Adults at Risk.en_US
dc.source.journaltitleBiological psychiatry global open scienceen_US
dc.source.countryUnited States
dc.description.institutionSUNY Downstateen_US
dc.description.departmentHenri Begleiter Neurodynamics Laboratoryen_US
dc.identifier.journalBiological psychiatry global open science

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© 2021 The Authors.
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