Polygenic contributions to alcohol use and alcohol use disorders across population-based and clinically ascertained samples

Emma C Johnson, Sandra Sanchez-Roige, Laura Acion, Mark J Adams, Kathleen K Bucholz, Grace Chan, Michael J Chao, David B Chorlian, Danielle M Dick, Howard J Edenberg, Tatiana Foroud, Caroline Hayward, Jon Heron, Victor Hesselbrock, Matthew Hickman, Kenneth S Kendler, Sivan Kinreich, John Kramer, Sally I-Chun Kuo, Samuel KupermanDongbing Lai, Andrew M McIntosh, Jacquelyn L Meyers, Martin H Plawecki, Bernice Porjesz, David Porteous, Marc A Schuckit, Jinni Su, Yong Zang, Abraham A Palmer, Arpana Agrawal, Toni-Kim Clarke, Alexis C Edwards

Research output: Contribution to journalArticle (Academic Journal)peer-review

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Abstract

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.

Original languageEnglish
JournalPsychological Medicine
Early online date20 Jan 2020
DOIs
Publication statusE-pub ahead of print - 20 Jan 2020

Keywords

  • alcohol consumption
  • alcohol dependence
  • alcohol use disorder
  • audit
  • genetics
  • GWAS
  • polygenic risk score

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