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The impact of sex, age at onset, recurrence, mode of ascertainment and medical complications on the family genetic risk score profiles for alcohol use disorder

Published online by Cambridge University Press:  08 October 2021

Kenneth S. Kendler Open the ORCID record for Kenneth S. Kendler [Opens in a new window] ,
Henrik Ohlsson ,
Jan Sundquist  and
Kristina Sundquist
Kenneth S. Kendler*
Affiliation:
Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA
Henrik Ohlsson
Affiliation:
Center for Primary Health Care Research, Lund University, Malmö, Sweden
Jan Sundquist
Affiliation:
Center for Primary Health Care Research, Lund University, Malmö, Sweden Department of Family Medicine and Community Health, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, USA Department of Functional Pathology, Center for Community-based Healthcare Research and Education (CoHRE), School of Medicine, Shimane University, Matsue, Japan
Kristina Sundquist
Affiliation:
Center for Primary Health Care Research, Lund University, Malmö, Sweden Department of Family Medicine and Community Health, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, USA Department of Functional Pathology, Center for Community-based Healthcare Research and Education (CoHRE), School of Medicine, Shimane University, Matsue, Japan
*
Author for correspondence: Kenneth S. Kendler, E-mail: Kenneth.Kendler@vcuhealth.org
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Abstract

Background

Alcohol use disorder (AUD) is clinically heterogeneous. We examine its potential genetic heterogeneity as a function of sex, age, clinical features and mode of ascertainment.

Methods

In the Swedish population born 1932–1995 (n = 5 829 952), we examined the genetic risk profiles for AUD, major depression (MD), anxiety disorders, bipolar disorder, drug use disorder (DUD), attention deficit-hyperactivity disorder (ADHD) and criminal behavior (CB) in 361 124 cases of AUD subdivided by sex, age at onset (AAO), recurrence, mode of ascertainment and medical complications. Family genetic risk scores (FGRS), calculated from 1st to 5th-degree relatives controlling of cohabitation, assesses genetic risk from phenotypes in the family, not from DNA variants.

Results

FGRS profiles differed modestly across sex with all scores higher in females. Differences were more pronounced for AAO and recurrence with the FGRS for AUD, DUD, ADHD and CB substantially higher in cases with early AAO or high recurrence rates. Genetic profiles differed considerably by mode of ascertainment, with higher FGRS for AUD and most other disorders in patients seen in hospital v. primary care settings. Cases of AUD with medical complications had higher FGRS for AUD. AUD cases comorbid with MD and DUD had higher FGRS risk for AUD, but this genetic may be less specific given increases in FGRS for multiple other disorders.

Conclusions

From a genetic perspective, AUD differs substantially as a function of AAO, recurrence, mode of ascertainment and patterns of comorbidity, suggesting caution in cross-sample comparisons of AUD cohorts that differ in these features.

Keywords

Alcohol use disorderheterogeneitygeneticsfamilial genetic risk scores
Type
Original Article
Information
Psychological Medicine , Volume 53 , Issue 5 , April 2023 , pp. 1732 - 1740
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Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press

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