Gene–environment correlations and causal effects of childhood maltreatment on physical and mental health: a genetically informed approach
Year: 2021
Type: review
Study design: Observational Study
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 disease, type 2 diabetes) or inflammation (C-reactive protein concentration). INTERPRETATION: 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. Our study identifies research avenues to inform the prevention of childhood maltreatment and its long-term effects. FUNDING: Wellcome Trust, UK Medical Research Council, Horizon 2020, National Institute of Mental Health, and National Institute for Health Research Biomedical Research Centre.
Source: The Lancet Psychiatry
Institutions: University of Cambridge, University of Bristol, MRC Integrative Epidemiology Unit, University of Edinburgh, Erasmus MC, Erasmus University Rotterdam, University of Cape Town, King's College London, University College London, University Hospitals Bristol NHS Foundation Trust, NIHR Bristol Biomedical Research Centre, University of California San Diego, VA San Diego Healthcare System, Center of Excellence for Stress and Mental Health, MRC Biostatistics Unit, Children's Hospital of Philadelphia, University of Pennsylvania, Leiden University Medical Center
Language: English
Topic: Child Abuse and Trauma
Subfield: Clinical Psychology
Field: Psychology
Domain: Social Sciences
Open Access status: hybrid
Estimated APC paid: $5,000
Funders: Wellcome Trust, Center of Excellence for Stress and Mental Health, National Institute for Health and Care Research, British Heart Foundation, Royal Society, University of Bristol, ZonMw, Erasmus Universiteit Rotterdam, Ministerie van Volksgezondheid, Welzijn en Sport, Erasmus Medisch Centrum, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, China Scholarship Council, Medical Research Council, Economic and Social Research Council, European Research Council, St Catharine's College, University of Cambridge, NIHR Cambridge Biomedical Research Centre, National Institute of Mental Health, H2020 Marie Skłodowska-Curie Actions
Awards: G1004914174, Genetics and causality: towards more accessible and more reliable Mendelian randomization investigations, G1222096694, NIHR Senior Investigator Award, G1866136476, Applying causal inference methods to investigate the impact of adverse childhood experiences on mental health, Common Variant Genetics of Autism and Autistic Traits (GWAS) Consortium, Large-scale integrative genomic studies of high-dimensional traits in cardiovascular diseases (renewal), Mechanisms of resilience to developmental stress in children and adolescents., Examining the aetiology, nature and consequences of depression in young people within a biosocial framework, The Avon Longitudinal Study of Parents and Children (ALSPAC): A multi- generation, longitudinal resource focusing on life course health and well- being., Stratifying Resilience and Depression Longitudinally (STRADL), NIHR Senior Investigator Award, G5154717229, G5317615622, UK Biobank (core renewal), G5707426241, G5796121737, Stratifying Resilience and Depression Longitudinally (STRADL), Causes, Consequences and Modification of Health Behaviour, The BHF Chair of Epidemiology and Medicine, Genetics and causality: towards more accessible and more reliable Mendelian randomization investigations, Large-scale integrative studies of risk factors in coronary heart disease: from discovery to application (renewal). (Joint funding with MRC), The Avon Longitudinal Study of Parents and Children (ALSPAC): A multi-generation, longitudinal resource focusing on life course health and well-being., Common Variant Genetics of Autism and Autistic Traits (GWAS) Consortium, Creating an adaptive screening tool for detecting neurocognitive deficits and psychopathology across the lifespan, LEaDing Fellows, Psychiatric Genomics Consortium for PTSD
OpenAlex ID: W3114167483