The Genetic Relationship Between Alcohol Consumption and Aspects of Problem Drinking in an Ascertained Sample

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dc.authoridKuperman, Samuel/0000-0002-5995-1981
dc.authoridDick, Danielle/0000-0002-1636-893X
dc.authoridSt. Pierre, Celine/0000-0001-5465-6601
dc.authoridKramer, John/0000-0002-1321-7087
dc.authoridBucholz, Kathleen/0000-0003-3794-0736
dc.authoridJohnson, Emma/0000-0003-0394-777X
dc.contributor.authorJohnson, Emma C.
dc.contributor.authorSt Pierre, Celine L.
dc.contributor.authorMeyers, Jacquelyn L.
dc.contributor.authorAliev, Fazil
dc.contributor.authorMcCutcheon, Vivia V.
dc.contributor.authorLai, Dongbing
dc.contributor.authorDick, Danielle M.
dc.date.accessioned2024-09-29T16:04:33Z
dc.date.available2024-09-29T16:04:33Z
dc.date.issued2019
dc.departmentKarabük Üniversitesien_US
dc.description.abstractBackground Genomewide association studies (GWAS) have begun to identify loci related to alcohol consumption, but little is known about whether this genetic propensity overlaps with specific indices of problem drinking in ascertained samples. Methods In 6,731 European Americans who had been exposed to alcohol, we examined whether polygenic risk scores (PRS) from a GWAS of weekly alcohol consumption in the UK Biobank predicted variance in 6 alcohol-related phenotypes: alcohol use, maximum drinks within 24 hours (MAXD), total score on the Self-Rating of the Effects of Ethanol Questionnaire (SRE-T), DSM-IV alcohol dependence (DSM4AD), DSM-5 alcohol use disorder symptom counts (DSM5AUDSX), and reduction/cessation of problematic drinking. We also examined the extent to which an single nucleotide polymorphism (rs1229984) in ADH1B, which is strongly associated with both alcohol consumption and dependence, contributed to the polygenic association with these phenotypes and whether PRS interacted with sex, age, or family history of alcoholism to predict alcohol-related outcomes. We performed mixed-effect regression analyses, with family membership and recruitment site included as random effects, as well as survival modeling of age of onset of DSM4AD. Results PRS for alcohol consumption significantly predicted variance in 5 of the 6 outcomes: alcohol use (Delta marginal R-2 = 1.39%, Delta area under the curve [AUC] = 0.011), DSM4AD (Delta marginal R-2 = 0.56%; Delta AUC = 0.003), DSM5AUDSX (Delta marginal R-2 = 0.49%), MAXD (Delta marginal R-2 = 0.31%), and SRE-T (Delta marginal R-2 = 0.22%). PRS were also associated with onset of DSM4AD (hazard ratio = 1.11, p = 2.08e-5). The inclusion of rs1229984 attenuated the effects of the alcohol consumption PRS, particularly for DSM4AD and DSM5AUDSX, but the PRS continued to exert an independent effect for all 5 alcohol measures (Delta marginal R-2 after controlling for ADH1B = 0.14 to 1.22%). Interactions between PRS and sex, age, or family history were nonsignificant. Conclusions Genetic propensity for typical alcohol consumption was associated with alcohol use and was also associated with 4 of the additional 5 outcomes, though the variance explained in this sample was modest. Future GWAS that focus on the multifaceted nature of AUD, which goes beyond consumption, might reveal additional information regarding the polygenic underpinnings of problem drinking.en_US
dc.description.sponsorshipNational Institutes of Health (NIH) from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) [U10AA008401]; National Institute on Drug Abuse; [MH109532]; [F32AA027435]en_US
dc.description.sponsorshipThe COGA (principal investigators: B. Porjesz, V. Hesselbrock, H. Edenberg, and L. Bierut) includes eleven different centers: University of Connecticut (V. Hesselbrock); Indiana University (H.J. Edenberg, J. Nurnberger Jr., T. Foroud, Y. Liu); University of Iowa (S. Kuperman, J. Kramer); SUNY Downstate (B. Porjesz); Washington University in St Louis (L. Bierut, J. Rice, K. Bucholz, A. Agrawal); University of California at San Diego (M. Schuckit); Rutgers University (J. Tischfield, A. Brooks); Department of Biomedical and Health Informatics, The Children's Hospital of Philadelphia, and Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA (L. Almasy); Virginia Commonwealth University (D. Dick); Icahn School of Medicine at Mount Sinai (A. Goate); and Howard University (R. Taylor). Other COGA collaborators include L. Bauer (University of Connecticut); J. McClintick, L. Wetherill, X. Xuei, D. Lai, S. O'Connor, M. Plawecki, and S. Lourens (Indiana University); G. Chan (University of Iowa; University of Connecticut); J. Meyers, D. Chorlian, C. Kamarajan, A. Pandey, and J. Zhang (SUNY Downstate); J.-C. Wang, M. Kapoor, and S. Bertelsen (Icahn School of Medicine at Mount Sinai); A. Anokhin, V. McCutcheon, and S. Saccone (Washington University); J. Salvatore, F. Aliev, and B. Cho (Virginia Commonwealth University); and Mark Kos (University of Texas Rio Grande Valley). A. Parsian and H. Chen are the NIAAA Staff Collaborators. We continue to be inspired by our memories of Henri Begleiter and Theodore Reich, founding PI and co-PI of COGA, and also owe a debt of gratitude to other past organizers of COGA, including Ting-Kai Li, P. Michael Conneally, Raymond Crowe, and Wendy Reich, for their critical contributions. This national collaborative study was supported by National Institutes of Health (NIH) Grant U10AA008401 from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the National Institute on Drug Abuse. This research was also supported by MH109532 (ECJ, AA, HJE) and F32AA027435 (ECJ).en_US
dc.identifier.doi10.1111/acer.14064
dc.identifier.endpage1125en_US
dc.identifier.issn2993-7175
dc.identifier.issue6en_US
dc.identifier.pmid30994927en_US
dc.identifier.scopus2-s2.0-85066147911en_US
dc.identifier.scopusqualityN/Aen_US
dc.identifier.startpage1113en_US
dc.identifier.urihttps://doi.org/10.1111/acer.14064
dc.identifier.urihttps://hdl.handle.net/20.500.14619/6199
dc.identifier.volume43en_US
dc.identifier.wosWOS:000472978100008en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherWileyen_US
dc.relation.ispartofAlcoholism-Clinical and Experimental Researchen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectAlcohol Dependenceen_US
dc.subjectAlcohol Consumptionen_US
dc.subjectPolygenic Risken_US
dc.subjectADH1Ben_US
dc.titleThe Genetic Relationship Between Alcohol Consumption and Aspects of Problem Drinking in an Ascertained Sampleen_US
dc.typeArticleen_US

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