Gene-environment correlations and causal effects of childhood maltreatment on physical and mental health: a genetically informed approach
Publication: The Lancet Psychiatry
Varun Warrier, Alex S F Kwong, Mannan Luo, Shareefa Dalvie, Jazz Croft, Hannah M Sallis, et al.
16 March 2021
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, the researchers aimed to delineate the sources of gene–environment correlation for childhood maltreatment and the causal relationship between childhood maltreatment and health.
They did a genome-wide association study meta-analysis of childhood maltreatment using data from the UK Biobank, Psychiatric Genomics Consortium, Avon Longitudinal Study of Parents and Children, Adolescent Brain Cognitive Development Study and Generation R.
Family-based and population-based polygenic score analyses were done to elucidate gene–environment correlation mechanisms. The team used genetic correlation and Mendelian randomisation analyses to identify shared genetics and test causal relationships between childhood maltreatment and mental and physical health conditions.
This meta-analysis of genome-wide association studies identified 14 independent loci associated with childhood maltreatment. The researchers identified high genetic overlap 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 disease, type 2 diabetes) or inflammation (C-reactive protein concentration).
Childhood maltreatment has a heritable component, with substantial genetic correlations among different operationalisations, subtypes, and retrospective and prospective reports of childhood maltreatment.
Family-based analyses point to a role of active and reactive gene–environment correlation, with equivocal support for passive correlation. Mendelian randomisation supports a (primarily bidirectional) causal role of childhood maltreatment on mental health, but not on physical health conditions. This study identifies research avenues to inform the prevention of childhood maltreatment and its long-term effects.