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 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

doi:10.1017/S0033291719004045

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

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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 language	English
Journal	Psychological Medicine
Early online date	20 Jan 2020
DOIs	https://doi.org/10.1017/S0033291719004045
Publication status	E-pub ahead of print - 20 Jan 2020

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Revised: 'Excessive drinking and alcohol related harms in Adulthood: ALSPAC at 24 MR/L022206/1'
Hickman, M. (Principal Investigator)
1/06/15 → 31/05/20
Project: Research

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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. (2020). Polygenic contributions to alcohol use and alcohol use disorders across population-based and clinically ascertained samples. Psychological Medicine. Advance online publication. https://doi.org/10.1017/S0033291719004045

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title = "Polygenic contributions to alcohol use and alcohol use disorders across population-based and clinically ascertained samples",

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.",

keywords = "alcohol consumption, alcohol dependence, alcohol use disorder, audit, genetics, GWAS, polygenic risk score",

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

year = "2020",

month = jan,

day = "20",

doi = "10.1017/S0033291719004045",

language = "English",

journal = "Psychological Medicine",

issn = "0033-2917",

publisher = "Cambridge University Press",

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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-C, 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, T-K & Edwards, AC 2020, 'Polygenic contributions to alcohol use and alcohol use disorders across population-based and clinically ascertained samples', Psychological Medicine. https://doi.org/10.1017/S0033291719004045

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

PY - 2020/1/20

Y1 - 2020/1/20

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 - alcohol consumption

KW - alcohol dependence

KW - alcohol use disorder

KW - audit

KW - genetics

KW - GWAS

KW - polygenic risk score

U2 - 10.1017/S0033291719004045

DO - 10.1017/S0033291719004045

M3 - Article (Academic Journal)

C2 - 31955720

SN - 0033-2917

JO - Psychological Medicine

JF - Psychological Medicine

ER -

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

Abstract

Keywords

UN SDGs

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Revised: 'Excessive drinking and alcohol related harms in Adulthood: ALSPAC at 24 MR/L022206/1'

Cite this