Evaluating risk for alcohol use disorder: Polygenic risk scores and family history

Dongbing Lai; Emma C Johnson; Sarah Colbert; Gayathri Pandey; Grace Chan; Lance Bauer; Meredith W Francis; Victor Hesselbrock; Chella Kamarajan; John Kramer; Weipeng Kuang; Sally Kuo; Samuel Kuperman; Yunlong Liu; Vivia McCutcheon; Zhiping Pang; Martin H Plawecki; Marc Schuckit; Jay Tischfield; Leah Wetherill; Yong Zang; Howard J Edenberg; Bernice Porjesz; Arpana Agrawal; Tatiana Foroud

doi:10.1111/acer.14772

Evaluating risk for alcohol use disorder: Polygenic risk scores and family history

Alcohol Clin Exp Res. 2022 Mar;46(3):374-383. doi: 10.1111/acer.14772. Epub 2022 Mar 10.

Authors

Dongbing Lai¹, Emma C Johnson², Sarah Colbert², Gayathri Pandey³, Grace Chan^{4

5}, Lance Bauer⁴, Meredith W Francis⁶, Victor Hesselbrock⁴, Chella Kamarajan³, John Kramer⁵, Weipeng Kuang³, Sally Kuo⁷, Samuel Kuperman⁵, Yunlong Liu¹, Vivia McCutcheon², Zhiping Pang⁸, Martin H Plawecki⁹, Marc Schuckit¹⁰, Jay Tischfield¹¹, Leah Wetherill¹, Yong Zang¹², Howard J Edenberg^{1

13}, Bernice Porjesz³, Arpana Agrawal², Tatiana Foroud¹

Affiliations

¹ Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
² Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri, USA.
³ Henri Begleiter Neurodynamics Lab, Department of Psychiatry, Downstate Medical Center, State University of New York, Brooklyn, New York, USA.
⁴ Department of Psychiatry, University of Connecticut School of Medicine, Farmington, Connecticut, USA.
⁵ Department of Psychiatry, University of Iowa Roy J and Lucille A Carver College of Medicine, Iowa City, Iowa, USA.
⁶ The Brown School of Social Work, Washington University School of Medicine, St Louis, Missouri, USA.
⁷ Department of Psychology, Virginia Commonwealth University, Richmond, Virginia, USA.
⁸ Department of Neuroscience and Cell Biology, Child Health Institute of New Jersey, Rutgers-Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA.
⁹ Department of Psychiatry, Indiana University School of Medicine, Indianapolis, Indiana, USA.
¹⁰ Department of Psychiatry, University of California, San Diego Medical School, San Diego, California, USA.
¹¹ Department of Genetics, Human Genetics Institute of New Jersey, Rutgers University, Piscataway, New Jersey, USA.
¹² Department of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, Indiana, USA.
¹³ Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA.

Abstract

Background: Early identification of individuals at high risk for alcohol use disorder (AUD) coupled with prompt interventions could reduce the incidence of AUD. In this study, we investigated whether Polygenic Risk Scores (PRS) can be used to evaluate the risk for AUD and AUD severity (as measured by the number of DSM-5 AUD diagnostic criteria met) and compared their performance with a measure of family history of AUD.

Methods: We studied individuals of European ancestry from the Collaborative Study on the Genetics of Alcoholism (COGA). DSM-5 diagnostic criteria were available for 7203 individuals, of whom 3451 met criteria for DSM-IV alcohol dependence or DSM-5 AUD and 1616 were alcohol-exposed controls aged ≥21 years with no history of AUD or drug dependence. Further, 4842 individuals had a positive first-degree family history of AUD (FH+), 2722 had an unknown family history (FH?), and 336 had a negative family history (FH-). PRS were derived from a meta-analysis of a genome-wide association study of AUD from the Million Veteran Program and scores from the problem subscale of the Alcohol Use Disorders Identification Test in the UK Biobank. We used mixed models to test the association between PRS and risk for AUD and AUD severity.

Results: AUD cases had higher PRS than controls with PRS increasing as the number of DSM-5 diagnostic criteria increased (p-values ≤ 1.85E^-05 ) in the full COGA sample, the FH+ subsample, and the FH? subsample. Individuals in the top decile of PRS had odds ratios (OR) for developing AUD of 1.96 (95% CI: 1.54 to 2.51, p-value = 7.57E^-08 ) and 1.86 (95% CI: 1.35 to 2.56, p-value = 1.32E^-04 ) in the full sample and the FH+ subsample, respectively. These values are comparable to previously reported ORs for a first-degree family history (1.91 to 2.38) estimated from national surveys. PRS were also significantly associated with the DSM-5 AUD diagnostic criterion count in the full sample, the FH+ subsample, and the FH? subsample (p-values ≤6.7E^-11 ). PRS remained significantly associated with AUD and AUD severity after accounting for a family history of AUD (p-values ≤6.8E^-10 ).

Conclusions: Both PRS and family history were associated with AUD and AUD severity, indicating that these risk measures assess distinct aspects of liability to AUD traits.

Keywords: DSM-5 alcohol use disorder diagnostic criterion count; alcohol use disorders; family history of AUD; polygenic risk scores.

Publication types

Meta-Analysis
Research Support, N.I.H., Extramural

MeSH terms

Alcohol Drinking / epidemiology
Alcoholism* / diagnosis
Alcoholism* / epidemiology
Alcoholism* / genetics
Diagnostic and Statistical Manual of Mental Disorders
Genome-Wide Association Study
Humans
Risk Factors

Abstract

Publication types

MeSH terms

Grants and funding