Gene-environment correlations and causal effects of childhood maltreatment on physical and mental health: a genetically informed approach.

Journal: The lancet. Psychiatry

Volume: 8

Issue: 5

Year of Publication: 2021

Affiliated Institutions:  Department of Psychiatry, University of Cambridge, Cambridge, UK. Electronic address: vw@medschl.cam.ac.uk. MRC Integrative Epidemiology Unit at the University of Bristol, University of Bristol, Bristol, UK; Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK; Division of Psychiatry, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK. Department of Psychology, Education and Child Studies, Erasmus University Rotterdam, Rotterdam, Netherlands; Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands. South Africa MRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa. Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK. MRC Integrative Epidemiology Unit at the University of Bristol, University of Bristol, Bristol, UK; Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK. Department of Clinical, Educational and Health Psychology, Division of Psychology and Language Sciences, University College London, London, UK; Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. MRC Integrative Epidemiology Unit at the University of Bristol, University of Bristol, Bristol, UK; School of Psychological Science, University of Bristol, Bristol, UK; NIHR Biomedical Research Centre at the University Hospitals Bristol NHS Foundation Trust and the University of Bristol, Bristol, UK. Department of Psychiatry, University of California San Diego, La Jolla, CA, USA; Center of Excellence for Stress and Mental Health, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA; Research Service, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA; Veterans Affairs San Diego Healthcare System, San Diego, CA, USA. MRC Biostatistics Unit, University of Cambridge, Cambridge, UK. MRC Biostatistics Unit, University of Cambridge, Cambridge, UK; Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA; Lifespan Brain Institute of the Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, PA, USA. Division of Psychiatry, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK; Centre for Cognitive Ageing and Cognitive Epidemiology, School of Philosophy, Psychology and Language Sciences, University of Edinburgh, Edinburgh, UK. Department of Psychology, Education and Child Studies, Erasmus University Rotterdam, Rotterdam, Netherlands; Department of Clinical, Educational and Health Psychology, Division of Psychology and Language Sciences, University College London, London, UK. Department of Child and Adolescent Psychiatry, Erasmus MC, Rotterdam, Netherlands; Department of Epidemiology, Erasmus MC, Rotterdam, Netherlands; Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, Netherlands.

Abstract summary 

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.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.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).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.Wellcome Trust, UK Medical Research Council, Horizon 2020, National Institute of Mental Health, and National Institute for Health Research Biomedical Research Centre.

Authors & Co-authors:  Warrier Varun V Kwong Alex S F ASF Luo Mannan M Dalvie Shareefa S Croft Jazz J Sallis Hannah M HM Baldwin Jessie J Munafò Marcus R MR Nievergelt Caroline M CM Grant Andrew J AJ Burgess Stephen S Moore Tyler M TM Barzilay Ran R McIntosh Andrew A van IJzendoorn Marinus H MH Cecil Charlotte A M CAM

Study Outcome 

Source Link: Visit source

Statistics
Citations :  Stoltenborgh M, Bakermans-Kranenburg MJ, Alink LRA, van IJzendoorn MH. The prevalence of child maltreatment across the globe: review of a series of meta-analyses. Child Abuse Rev. 2015;24:37–50.
Authors :  16
Identifiers
Doi : 10.1016/S2215-0366(20)30569-1
SSN : 2215-0374
Study Population
Male,Female
Mesh Terms
Adolescent
Other Terms
Study Design
Longitudinal Study,Cross Sectional Study
Study Approach
Country of Study
Publication Country
England