| Title: | Polygenic contributions to alcohol use and alcohol use disorders across population-based and clinically ascertained samples |
| Journal: | Psychological Medicine |
| Published: | 20 Jan 2020 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/31955720/ |
| DOI: | https://doi.org/10.1017/s0033291719004045 |
| URL: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7405725 |
| Citations: | 20 (7 in last 2 years) as of 8 Aug 2024 |
Publication 5566
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Abstract
BACKGROUND: Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds.</p>
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.</p>
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).</p>
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.</p>
8 Keywords
- Alcohol Drinking
- Alcoholism
- Cohort Studies
- Genome-Wide Association Study
- Humans
- Longitudinal Studies
- Phenotype
- Scotland
33 Authors
- 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 Kuperman
- Dongbing 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
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