Evidence map›Paper›PMID 33740410›Full record

SynthesisThe lancet. Psychiatry2021

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

Varun Warrier, Alex S F Kwong, Mannan Luo, Shareefa Dalvie, Jazz Croft, Hannah M Sallis, Jessie Baldwin, Marcus R Munafò, Caroline M Nievergelt, Andrew J Grant and 6 more

Erratum issuedAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in The lancet. Psychiatry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 125 papers, 8 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
125citing papers in PubMed, 8 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

125 citing papers in PubMed, 8 syntheses or guidelines pooled it.

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65 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors.

Varun WarrierDepartment of Psychiatry, University of Cambridge, Cambridge, UK. Electronic address: vw260@medschl.cam.ac.uk.
Alex S F KwongMRC 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.
Mannan LuoDepartment of Psychology, Education and Child Studies, Erasmus University Rotterdam, Rotterdam, Netherlands; Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands.
Shareefa DalvieSouth Africa MRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
Jazz CroftDepartment of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Hannah M SallisMRC 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.
Jessie BaldwinDepartment 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.
Marcus R MunafòMRC 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.
Caroline M NievergeltDepartment 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.
Andrew J GrantMRC Biostatistics Unit, University of Cambridge, Cambridge, UK.
Stephen BurgessMRC Biostatistics Unit, University of Cambridge, Cambridge, UK; Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Tyler M MooreDepartment 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.
Ran BarzilayDepartment 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.
Andrew McIntoshDivision 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.
Marinus H van IJzendoornDepartment 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.
Charlotte A M CecilDepartment 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.

Funding

Psychiatric Genomics Consortium for PTSDR01MH106595 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KARESTAN C KOENEN, Caroline M Nievergelt · 2016 to 2026
$8.4M
Creating an adaptive screening tool for detecting neurocognitive deficits and psychopathology across the lifespanR01MH117014 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI GUR, RUBEN C. · 2019 to 2022
$2.9M
Mechanisms of resilience to developmental stress in children and adolescents.K23MH120437 · NIMH · CHILDREN'S HOSP OF PHILADELPHIA · PI BARZILAY, RAN · 2019 to 2022
$775k
British Heart Foundation CH/12/2/29428British Heart Foundation RG/13/13/30194British Heart Foundation RG/18/13/33946Medical Research Council MC_PC_17228Medical Research Council MC_QA137853Medical Research Council MC_UU_00002/7Medical Research Council MC_UU_00011/7NIMH NIH HHS K23 MH120437NIMH NIH HHS R01 MH106595NIMH NIH HHS R01 MH117014Wellcome Trust 104036Wellcome Trust 204623Wellcome Trust 214322Wellcome Trust 217065
6 · The paper itself

Abstract

backgroundChildhood 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.

methodsWe 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.

findingsOur 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).

interpretationChildhood 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.

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

Indexed as

Gene-Environment InteractionAdolescentAdultAdult Survivors of Child AbuseAgedAged, 80 and overDatabases, FactualEuropeFemaleGenome-Wide Association StudyHumansLongitudinal StudiesMaleMental DisordersMental HealthMiddle Aged

Identifiers

PMID33740410
PMCPMC8055541

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.