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

Abstract

BackgroundStudies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds.MethodsWe 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.ResultsIn 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).ConclusionsAUDIT-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 (US)
JournalPsychological Medicine
DOIs
StateAccepted/In press - 2020

Keywords

  • AUDIT
  • Alcohol consumption
  • GWAS
  • alcohol dependence
  • alcohol use disorder
  • genetics
  • polygenic risk score

ASJC Scopus subject areas

  • Applied Psychology
  • Psychiatry and Mental health

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    Johnson, E. C., Sanchez-Roige, S., Acion, L., Adams, M. J., Bucholz, K. K., Chan, G., Chao, M. J., Chorlian, D. B., Dick, D. M., Edenberg, H. J., Foroud, T., Hayward, C., Heron, J., Hesselbrock, V., Hickman, M., Kendler, K. S., Kinreich, S., Kramer, J., Kuo, S. I. C., ... Edwards, A. C. (Accepted/In press). Polygenic contributions to alcohol use and alcohol use disorders across population-based and clinically ascertained samples. Psychological Medicine. https://doi.org/10.1017/S0033291719004045