TY - JOUR
T1 - Polygenic contributions to alcohol use and alcohol use disorders across population-based and clinically ascertained samples
AU - Johnson, Emma C.
AU - Sanchez-Roige, Sandra
AU - Acion, Laura
AU - Adams, Mark J.
AU - Bucholz, Kathleen K.
AU - Chan, Grace
AU - Chao, Michael J.
AU - Chorlian, David B.
AU - Dick, Danielle M.
AU - Edenberg, Howard J.
AU - Foroud, Tatiana
AU - Hayward, Caroline
AU - Heron, Jon
AU - Hesselbrock, Victor
AU - Hickman, Matthew
AU - Kendler, Kenneth S.
AU - Kinreich, Sivan
AU - Kramer, John
AU - Kuo, Sally I.Chun
AU - Kuperman, Samuel
AU - Lai, Dongbing
AU - Mcintosh, Andrew M.
AU - Meyers, Jacquelyn L.
AU - Plawecki, Martin H.
AU - Porjesz, Bernice
AU - Porteous, David
AU - Schuckit, Marc A.
AU - Su, Jinni
AU - Zang, Yong
AU - Palmer, Abraham A.
AU - Agrawal, Arpana
AU - Clarke, Toni Kim
AU - Edwards, Alexis C.
N1 - Publisher Copyright:
Copyright © 2020 The Author(s). Published by Cambridge University Press.
PY - 2021/5
Y1 - 2021/5
N2 - 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.
AB - 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.
KW - AUDIT
KW - Alcohol consumption
KW - GWAS
KW - alcohol dependence
KW - alcohol use disorder
KW - genetics
KW - polygenic risk score
UR - http://www.scopus.com/inward/record.url?scp=85078440682&partnerID=8YFLogxK
U2 - 10.1017/S0033291719004045
DO - 10.1017/S0033291719004045
M3 - Review article
C2 - 31955720
AN - SCOPUS:85078440682
SN - 0033-2917
VL - 51
SP - 1147
EP - 1156
JO - Psychological medicine
JF - Psychological medicine
IS - 7
ER -