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Heritable Composite Phenotypes Defined by Combinations of Conduct Problem, Depression, and Temperament Features: Contributions to risk for Alcohol Problems

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Abstract

The genetic architectures underlying symptoms of conduct problems and depression have largely been examined separately and without incorporating temperament, despite evidence for their genetic overlap. We examined how symptoms and temperament dimensions were transmitted together in families to identify highly heritable composite phenotypes, and how these composite phenotypes predicted alcohol outcomes in young adulthood. Participants (N = 486) were drawn from the third generation of families oversampled for alcohol use disorder in the first generation. Conduct problems, depression, and temperament were reported at 11–19 years old and alcohol outcomes at 18–26 years old. Using principal components of heritability analysis, we found seven highly heritable composite phenotypes, five of which predicted alcohol outcomes: three characterized by co-occurring conduct problems and depression and two by conduct problems. Novel composite phenotypes that were characterized by both conduct problems and depression showed different types of symptoms, temperament features, and genetic underpinnings. Children manifesting differing composite phenotypes might benefit from distinct treatments based on their unique etiologies.

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Availability of Data and Materials

The code for conducting study analyses is provided at https://github.com/franceswang3/Principal-Components-of-Heritability-Project.

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Funding

This research was supported by R01 AA016213 from NIAAA (Chassin) and K01 AA027757 from NIAAA (Wang).

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Authors and Affiliations

  1. Department of Psychiatry, University of Pittsburgh, 3811 O’Hara St, Pittsburgh, PA, 15213, USA

    Frances L. Wang, Lambertus Klei, Bernie Devlin & Brooke S.G. Molina

  2. Department of Psychology, Arizona State University, Tempe, AZ, 85281, USA

    Laurie Chassin

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  1. Frances L. Wang
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  2. Lambertus Klei
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  3. Bernie Devlin
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  4. Brooke S.G. Molina
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  5. Laurie Chassin
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Contributions

All authors contributed to the study conception and design. Analyses were performed by Frances Wang, Lambertus Klei, and Bernie Devlin. The first draft of the manuscript was written by Frances Wang and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Data collection was performed by Laurie Chassin.

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Correspondence to Frances L. Wang.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The original study was approved by Arizona State University’s institutional review board.

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Wang, F.L., Klei, L., Devlin, B. et al. Heritable Composite Phenotypes Defined by Combinations of Conduct Problem, Depression, and Temperament Features: Contributions to risk for Alcohol Problems. Res Child Adolesc Psychopathol 52, 535–550 (2024). https://doi.org/10.1007/s10802-023-01129-x

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