Polygenic contributions to alcohol use and alcohol use disorders across population-based and clinically ascertained samples.
Keyword
AUDITAlcohol consumption
GWAS
alcohol dependence
alcohol use disorder
genetics
polygenic risk score
Journal title
Psychological medicineDate Published
2020-01-20Publication Volume
51Publication Issue
7Publication Begin page
1147Publication End page
1156Metadata
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Background: Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds. Methods: We examined whether polygenic risk scores (PRS) for consumption and problem subscales of the Alcohol Use Disorders Identification Test (AUDIT-C, AUDIT-P) in the UK Biobank (UKB; N = 121 630) correlate with alcohol outcomes in four independent samples: an ascertained cohort, the Collaborative Study on the Genetics of Alcoholism (COGA; N = 6850), and population-based cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC; N = 5911), Generation Scotland (GS; N = 17 461), and an independent subset of UKB (N = 245 947). Regression models and survival analyses tested whether the PRS were associated with the alcohol-related outcomes. Results: In COGA, AUDIT-P PRS was associated with alcohol dependence, AUD symptom count, maximum drinks (R2 = 0.47-0.68%, p = 2.0 × 10-8-1.0 × 10-10), and increased likelihood of onset of alcohol dependence (hazard ratio = 1.15, p = 4.7 × 10-8); AUDIT-C PRS was not an independent predictor of any phenotype. In ALSPAC, the AUDIT-C PRS was associated with alcohol dependence (R2 = 0.96%, p = 4.8 × 10-6). In GS, AUDIT-C PRS was a better predictor of weekly alcohol use (R2 = 0.27%, p = 5.5 × 10-11), while AUDIT-P PRS was more associated with problem drinking (R2 = 0.40%, p = 9.0 × 10-7). Lastly, AUDIT-P PRS was associated with ICD-based alcohol-related disorders in the UKB subset (R2 = 0.18%, p < 2.0 × 10-16). Conclusions: AUDIT-P PRS was associated with a range of alcohol-related phenotypes across population-based and ascertained cohorts, while AUDIT-C PRS showed less utility in the ascertained cohort. We show that AUDIT-P is genetically correlated with both use and misuse and demonstrate the influence of ascertainment schemes on PRS analyses.Citation
Johnson EC, Sanchez-Roige S, Acion L, Adams MJ, Bucholz KK, Chan G, Chao MJ, Chorlian DB, Dick DM, Edenberg HJ, Foroud T, Hayward C, Heron J, Hesselbrock V, Hickman M, Kendler KS, Kinreich S, Kramer J, Kuo SI, Kuperman S, Lai D, McIntosh AM, Meyers JL, Plawecki MH, Porjesz B, Porteous D, Schuckit MA, Su J, Zang Y, Palmer AA, Agrawal A, Clarke TK, Edwards AC. Polygenic contributions to alcohol use and alcohol use disorders across population-based and clinically ascertained samples. Psychol Med. 2021 May;51(7):1147-1156. doi: 10.1017/S0033291719004045. Epub 2020 Jan 20. PMID: 31955720; PMCID: PMC7405725.DOI
10.1017/S0033291719004045Scopus Count
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