Associations between alcohol use disorder polygenic score and remission in participants from high-risk families and the Indiana Biobank

Dongbing Lai; Sally I-Chun Kuo; Leah Wetherill; Fazil Aliev; Michael Zhang; Abreu Marco; Tae-Hwi Schwantes-An; Danielle Dick; Meredith W Francis; Emma C Johnson; Chella Kamarajan; Sivan Kinreich; Samuel Kuperman; Jacquelyn Meyers; John I Nurnberger; Yunlong Liu; Howard J Edenberg; Bernice Porjesz; Arpana Agrawal; Tatiana Foroud; Marc Schuckit; Martin H Plawecki; Kathleen K Bucholz; Vivia V McCutcheon

doi:10.1111/acer.15239

Associations between alcohol use disorder polygenic score and remission in participants from high-risk families and the Indiana Biobank

Alcohol Clin Exp Res (Hoboken). 2024 Feb;48(2):283-294. doi: 10.1111/acer.15239. Epub 2023 Dec 12.

Authors

Dongbing Lai¹, Sally I-Chun Kuo², Leah Wetherill¹, Fazil Aliev², Michael Zhang¹, Abreu Marco¹, Tae-Hwi Schwantes-An¹, Danielle Dick², Meredith W Francis³, Emma C Johnson⁴, Chella Kamarajan⁵, Sivan Kinreich⁵, Samuel Kuperman⁶, Jacquelyn Meyers⁵, John I Nurnberger^{1

7}, Yunlong Liu¹, Howard J Edenberg^{1

8}, Bernice Porjesz⁵, Arpana Agrawal⁴, Tatiana Foroud¹, Marc Schuckit⁹, Martin H Plawecki⁷, Kathleen K Bucholz⁴, Vivia V McCutcheon⁴

Affiliations

¹ Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
² Department of Psychiatry, Robert Wood Johnson Medical School, Rutgers University, Piscataway, New Jersey, USA.
³ School of Social Work, Virginia Commonwealth University, Richmond, Virginia, USA.
⁴ Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.
⁵ Henri Begleiter Neurodynamics Lab, Department of Psychiatry, SUNY Downstate Health Science University, New York, New York, USA.
⁶ Department of Psychiatry, University of Iowa Roy J and Lucille A Carver College of Medicine, Iowa City, Iowa, USA.
⁷ Department of Psychiatry, Indiana University School of Medicine, Indianapolis, Indiana, USA.
⁸ Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
⁹ Department of Psychiatry, University of California, San Diego Medical School, San Diego, California, USA.

PMID: 38054532
PMCID: PMC10922306 (available on 2025-02-01)
DOI: 10.1111/acer.15239

Abstract

Background: In the United States, ~50% of individuals who meet criteria for alcohol use disorder (AUD) during their lifetimes do not remit. We previously reported that a polygenic score for AUD (PGS_AUD ) was positively associated with AUD severity as measured by DSM-5 lifetime criterion count, and AUD severity was negatively associated with remission. Thus, we hypothesized that PGS_AUD would be negatively associated with remission.

Methods: Individuals of European (EA) and African ancestry (AA) from the Collaborative Study on the Genetics of Alcoholism (COGA) who met lifetime criteria for AUD, and two EA cohorts ascertained for studies of liver diseases and substance use disorders from the Indiana Biobank were included. In COGA, 12-month remission was defined as any period of ≥12 consecutive months without meeting AUD criteria except craving and was further categorized as abstinent and non-abstinent. In the Indiana Biobank, remission was defined based on ICD codes and could not be further distinguished as abstinent or non-abstinent. Sex and age were included as covariates. COGA analyses included additional adjustment for AUD severity, family history of remission, and AUD treatment history.

Results: In COGA EA, PGS_AUD was negatively associated with 12-month and non-abstinent remission (p ≤ 0.013, βs between -0.15 and -0.10) after adjusting for all covariates. In contrast to the COGA findings, PGS_AUD was positively associated with remission (p = 0.004, β = 0.28) in the Indiana Biobank liver diseases cohort but not in the Indiana Biobank substance use disorder cohort (p = 0.17, β = 0.15).

Conclusions: PGS_AUD was negatively associated with 12-month and non-abstinent remission in COGA EA, independent of behavioral measures of AUD severity and family history of remission. The discrepant results in COGA and the Indiana Biobank could reflect different ascertainment strategies: the Indiana Biobank participants were older and had higher rates of liver disease, suggesting that these individuals remitted due to alcohol-related health conditions that manifested in later life.

Keywords: alcohol use disorder severity; alcohol use disorder treatment history; family history of remission; polygenic score; remission.

Abstract

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