1. Gene–environment correlations and causal effects of childhood maltreatment on physical and mental health
- Author
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Varun Warrier, Alex S.F. Kwong, M. (Mannan) Luo, Shareefa Dalvie, Jazz Croft, Hannah M. Sallis, Jessie Baldwin, Marcus R. Munafò, Caroline M. Nievergelt, Andrew J. Grant, Stephen Burgess, Tyler M. Moore, Ran Barzilay, Andrew McIntosh, Marinus H. van IJzendoorn, C.A.M. (Charlotte) Cecil, Varun Warrier, Alex S.F. Kwong, M. (Mannan) Luo, Shareefa Dalvie, Jazz Croft, Hannah M. Sallis, Jessie Baldwin, Marcus R. Munafò, Caroline M. Nievergelt, Andrew J. Grant, Stephen Burgess, Tyler M. Moore, Ran Barzilay, Andrew McIntosh, Marinus H. van IJzendoorn, and C.A.M. (Charlotte) Cecil
- Abstract
Background: Childhood maltreatment is associated with poor mental and physical health. However, the mechanisms of gene–environment correlations and the potential causal effects of childhood maltreatment on health are unknown. Using genetics, we aimed to delineate the sources of gene–environment correlation for childhood maltreatment and the causal relationship between childhood maltreatment and health. Methods: We did a genome-wide association study meta-analysis of childhood maltreatment using data from the UK Biobank (n=143 473), Psychiatric Genomics Consortium (n=26 290), Avon Longitudinal Study of Parents and Children (n=8346), Adolescent Brain Cognitive Development Study (n=5400), and Generation R (n=1905). We included individuals who had phenotypic and genetic data available. We investigated single nucleotide polymorphism heritability and genetic correlations among different subtypes, operationalisations, and reports of childhood maltreatment. Family-based and population-based polygenic score analyses were done to elucidate gene–environment correlation mechanisms. We used genetic correlation and Mendelian randomisation analyses to identify shared genetics and test causal relationships between childhood maltreatment and mental and physical health conditions. Findings: Our meta-analysis of genome-wide association studies (N=185 414) identified 14 independent loci associated with childhood maltreatment (13 novel). We identified high genetic overlap (genetic correlations 0·24–1·00) among different maltreatment operationalisations, subtypes, and reporting methods. Within-family analyses provided some support for active and reactive gene–environment correlation but did not show the absence of passive gene–environment correlation. Robust Mendelian randomisation suggested a potential causal role of childhood maltreatment in depression (unidirectional), as well as both schizophrenia and ADHD (bidirectional), but not in physical health conditions (coronary artery dis
- Published
- 2021
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