Journal article
Evaluating risk for alcohol use disorder: Polygenic risk scores and family history
Alcoholism, clinical and experimental research, Vol.46(3), pp.374-383
03/2022
DOI: 10.1111/acer.14772
PMCID: PMC8928056
PMID: 35267208
Abstract
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.
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.
AUD cases had higher PRS than controls with PRS increasing as the number of DSM-5 diagnostic criteria increased (p-values ≤ 1.85E
) 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
) and 1.86 (95% CI: 1.35 to 2.56, p-value = 1.32E
) 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
). PRS remained significantly associated with AUD and AUD severity after accounting for a family history of AUD (p-values ≤6.8E
).
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.
Details
- Title: Subtitle
- Evaluating risk for alcohol use disorder: Polygenic risk scores and family history
- Creators
- Dongbing Lai - Indiana UniversityEmma C Johnson - Washington University in St. LouisSarah Colbert - Washington University in St. LouisGayathri Pandey - SUNY Downstate Health Sciences UniversityGrace Chan - University of ConnecticutLance Bauer - University of ConnecticutMeredith W Francis - Washington University in St. LouisVictor Hesselbrock - University of ConnecticutChella Kamarajan - SUNY Downstate Health Sciences UniversityJohn Kramer - University of IowaWeipeng Kuang - SUNY Downstate Health Sciences UniversitySally Kuo - Virginia Commonwealth UniversitySamuel Kuperman - University of IowaYunlong Liu - Indiana UniversityVivia McCutcheon - Washington University in St. LouisZhiping Pang - Department of Neuroscience and Cell Biology, Child Health Institute of New Jersey, Rutgers-Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA.Martin H Plawecki - Indiana UniversityMarc Schuckit - University of California San Diego Medical CenterJay Tischfield - Rutgers, The State University of New JerseyLeah Wetherill - Indiana UniversityYong Zang - Indiana UniversityHoward J Edenberg - Indiana UniversityBernice Porjesz - SUNY Downstate Health Sciences UniversityArpana Agrawal - Washington University in St. LouisTatiana Foroud - Indiana University
- Resource Type
- Journal article
- Publication Details
- Alcoholism, clinical and experimental research, Vol.46(3), pp.374-383
- DOI
- 10.1111/acer.14772
- PMID
- 35267208
- PMCID
- PMC8928056
- NLM abbreviation
- Alcohol Clin Exp Res
- ISSN
- 0145-6008
- eISSN
- 1530-0277
- Publisher
- Wiley
- Grant note
- U01 MH109532 / NIMH NIH HHS U10 AA008401 / NIAAA NIH HHS K02 DA032573 / NIDA NIH HHS K01 DA051759 / NIDA NIH HHS T32 DA015035 / NIDA NIH HHS
- Language
- English
- Date published
- 03/2022
- Academic Unit
- Psychiatry
- Record Identifier
- 9984293651702771
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