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Differences in genetic risk score profiles for drug use disorder, major depression, and ADHD as a function of sex, age at onset, recurrence, mode of ascertainment, and treatment

Published online by Cambridge University Press:  31 January 2022

Kenneth S. Kendler Open the ORCID record for Kenneth S. Kendler [Opens in a new window] ,
Henrik Ohlsson ,
Silviu Bacanu ,
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
Silviu Bacanu
Affiliation:
Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA
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
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
*
Author for correspondence: Kenneth S. Kendler, E-mail: Kenneth.Kendler@vcuhealth.org
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Abstract

Background

Do genetic risk profiles for drug use disorder (DUD), major depression (MD), and attention-deficit hyperactivity disorder (ADHD) differ substantially as a function of sex, age at onset (AAO), recurrence, mode of ascertainment, and treatment?

Methods

Family genetic risk scores (FGRS) for MD, anxiety disorders, bipolar disorder, schizophrenia, alcohol use disorder, DUD, ADHD, and autism-spectrum disorder were calculated from 1st–5th degree relatives in the Swedish population born 1932–1995 (n = 5 829 952). Profiles of these FGRS were obtained and compared across various subgroups of DUD, MD, and ADHD cases.

Results

Differences in FGRS profiles for DUD, MD, and ADHD by sex were modest, but they varied substantially by AAO, recurrence, ascertainment, and treatment with scores typically higher in cases with greater severity (e.g. early AAO, high recurrence, ascertainment in high intensity clinical settings, and treatment). However, severity was not always related to purer genetic profiles, as genetic risk for many disorders often increased together. However, some results, such as by mode of ascertainment from different Swedish registries, produced qualitative differences in FGRS profiles.

Conclusions

Differences in FGRS profiles for DUD, MD, and ADHD varied substantially by AAO, recurrence, ascertainment, and treatment. Replication of psychiatric studies, particularly those examining genetic factors, may be difficult unless cases are matched not only by diagnosis but by important clinical characteristics. Genetic correlations between psychiatric disorders could arise through one disorder impacting on the patterns of ascertainment for the other, rather than from the direct effects of shared genetic liabilities.

Keywords

Major depressiondrug use disorderattention-deficit-hyperactivity disordergeneticsage at onsetrecurrence
Type
Original Article
Information
Psychological Medicine , Volume 53 , Issue 8 , June 2023 , pp. 3448 - 3460
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Copyright
Copyright © The Author(s), 2022. Published by Cambridge University Press

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