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Polygenic risk for autism, attention-deficit hyperactivity disorder, schizophrenia, major depressive disorder, and neuroticism is associated with the experience of childhood abuse

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Abstract

People who experience childhood abuse are at increased risk of mental illness. Twin studies suggest that inherited genetic risk for mental illness may account for some of these associations. Yet, the hypothesis that individuals who have experienced childhood abuse may carry genetic loading for mental illness has never been tested with genetic data. Using polygenic risk scores for six psychiatric disorders—attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BPD), major depressive disorder (MDD), neuroticism, and schizophrenia—we tested whether genetic risk for mental illness was associated with increased risk of experiencing three types of childhood abuse: physical/emotional abuse, physical assault, and sexual abuse, in a cohort of white non-Hispanic women (n = 11,315). ADHD and MDD genetic risk scores were associated with a higher risk of experiencing each type of childhood abuse, while neuroticism, schizophrenia, BPD, and ASD genetic scores were associated with a higher risk of experiencing physical/emotional abuse and physical assault, but not sexual abuse. Sensitivity analyses examining potential bias from the differential recall of childhood trauma, parental socioeconomic status, and population stratification were consistent with the main findings. A one-standard-deviation increase in genetic risk for mental illness was associated with a modestly elevated risk of experiencing childhood abuse (OR range: 1.05–1.19). Therefore, inherited genetic risk may partly account for the association of childhood abuse with mental illness. In addition, future treatments for mental illness will benefit from taking into consideration the co-occurrence of childhood trauma and genetic loading.

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Fig. 1: Potential genetic pathways account for the correlation between risk for mental health disorders and childhood abuse.
Fig. 2: Correlations between polygenic risk scores for mental health.
Fig. 3: Odds ratios and 95% confidence intervals (CI) associated with a one-standard-deviation increase in each mental health PRS for being in a higher level of childhood abuse adjusted for parental education, parental occupation, genomic assay, and ten GWAS principal components.
Fig. 4: Odds ratios and 95% confidence intervals (CI) associated with a one-standard-deviation increase in the MDD and neuroticism PRS for being in a higher level of childhood abuse, adjusted for parental education, parental occupation, genomic assay, and ten GWAS principal components among all participants (Nphysical/emotional abuse = 11,315, Nphysical assault = 11,322, Nsexual abuse = 11,317) and among those with no probable depression (n = 7994).

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Acknowledgements

This research was funded in part by R01HD094725 (to ALR). The Nurses’ Health Study II is funded by U01 CA176726. We would like to thank the participants and staff of the NHS2 for their valuable contributions and acknowledge the Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital for its management of the NHS2. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Authors and Affiliations

  1. Department of Epidemiology, Columbia University Mailman School of Public Health, New York, NY, USA

    Andrew Ratanatharathorn

  2. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Karestan C. Koenen, Lori B. Chibnik, Marc G. Weisskopf & Janet W. Rich-Edwards

  3. Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA

    Karestan C. Koenen

  4. Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA

    Karestan C. Koenen

  5. Department of Neurology, Massachusetts General Hospital, Boston, MA, USA

    Lori B. Chibnik

  6. Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Marc G. Weisskopf & Andrea L. Roberts

  7. Division of Women’s Health, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA

    Janet W. Rich-Edwards

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Ratanatharathorn, A., Koenen, K.C., Chibnik, L.B. et al. Polygenic risk for autism, attention-deficit hyperactivity disorder, schizophrenia, major depressive disorder, and neuroticism is associated with the experience of childhood abuse. Mol Psychiatry 26, 1696–1705 (2021). https://doi.org/10.1038/s41380-020-00996-w

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