The Genetic Relationship Between Alcohol Consumption and Aspects of Problem Drinking in an Ascertained Sample
dc.authorid | Kuperman, Samuel/0000-0002-5995-1981 | |
dc.authorid | Dick, Danielle/0000-0002-1636-893X | |
dc.authorid | St. Pierre, Celine/0000-0001-5465-6601 | |
dc.authorid | Kramer, John/0000-0002-1321-7087 | |
dc.authorid | Bucholz, Kathleen/0000-0003-3794-0736 | |
dc.authorid | Johnson, Emma/0000-0003-0394-777X | |
dc.contributor.author | Johnson, Emma C. | |
dc.contributor.author | St Pierre, Celine L. | |
dc.contributor.author | Meyers, Jacquelyn L. | |
dc.contributor.author | Aliev, Fazil | |
dc.contributor.author | McCutcheon, Vivia V. | |
dc.contributor.author | Lai, Dongbing | |
dc.contributor.author | Dick, Danielle M. | |
dc.date.accessioned | 2024-09-29T16:04:33Z | |
dc.date.available | 2024-09-29T16:04:33Z | |
dc.date.issued | 2019 | |
dc.department | Karabük Üniversitesi | en_US |
dc.description.abstract | Background 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.sponsorship | National 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.sponsorship | The 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.doi | 10.1111/acer.14064 | |
dc.identifier.endpage | 1125 | en_US |
dc.identifier.issn | 2993-7175 | |
dc.identifier.issue | 6 | en_US |
dc.identifier.pmid | 30994927 | en_US |
dc.identifier.scopus | 2-s2.0-85066147911 | en_US |
dc.identifier.scopusquality | N/A | en_US |
dc.identifier.startpage | 1113 | en_US |
dc.identifier.uri | https://doi.org/10.1111/acer.14064 | |
dc.identifier.uri | https://hdl.handle.net/20.500.14619/6199 | |
dc.identifier.volume | 43 | en_US |
dc.identifier.wos | WOS:000472978100008 | en_US |
dc.identifier.wosquality | Q2 | en_US |
dc.indekslendigikaynak | Web of Science | en_US |
dc.indekslendigikaynak | Scopus | en_US |
dc.indekslendigikaynak | PubMed | en_US |
dc.language.iso | en | en_US |
dc.publisher | Wiley | en_US |
dc.relation.ispartof | Alcoholism-Clinical and Experimental Research | en_US |
dc.relation.publicationcategory | Makale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı | en_US |
dc.rights | info:eu-repo/semantics/openAccess | en_US |
dc.subject | Alcohol Dependence | en_US |
dc.subject | Alcohol Consumption | en_US |
dc.subject | Polygenic Risk | en_US |
dc.subject | ADH1B | en_US |
dc.title | The Genetic Relationship Between Alcohol Consumption and Aspects of Problem Drinking in an Ascertained Sample | en_US |
dc.type | Article | en_US |