Genetic decomposition of the heritable component of reported childhood maltreatment

Abigail ter Kuile; Christopher Hübel; Rosa Cheesman; Jonathan Coleman; Alicia Peel; Daniel F Levey; Murray B. Stein; Joel Gelernter; Christopher Rayner; Thalia Eley; Gerome Breen

doi:10.1016/j.bpsgos.2023.03.003

Genetic decomposition of the heritable component of reported childhood maltreatment

Abigail ter Kuile, Christopher Hübel, Rosa Cheesman, Jonathan Coleman, Alicia Peel, Daniel F Levey, Murray B. Stein, Joel Gelernter, Christopher Rayner, Thalia Eley, Gerome Breen^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

4 Citations (Scopus)

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Abstract

Background

Decades of research have shown that environmental exposures, including self-reports of trauma, are partly heritable. Heritable characteristics may influence exposure to and interpretations of environmental factors. Identifying heritable factors associated with self-reported trauma could improve our understanding of vulnerability to exposure and the interpretation of life events.

Methods

We used genome-wide association study summary statistics of childhood maltreatment, defined as reporting of abuse (emotional, sexual, and physical) and neglect (emotional and physical) (N = 185,414 participants). We calculated genetic correlations (rg) between reported childhood maltreatment and 576 traits to identify phenotypes that might explain the heritability of reported childhood maltreatment, retaining those with |rg| > 0.25. We specified multiple regression models using genomic structural equation modeling to detect residual genetic variance in childhood maltreatment after accounting for genetically correlated traits.

Results

In 2 separate models, the shared genetic component of 12 health and behavioral traits and 7 psychiatric disorders accounted for 59% and 56% of heritability due to common genetic variants (single nucleotide polymorphism–based heritability [h2SNP]) of childhood maltreatment, respectively. Genetic influences on h2SNP of childhood maltreatment were generally accounted for by a shared genetic component across traits. The exceptions to this were general risk tolerance, subjective well-being, posttraumatic stress disorder, and autism spectrum disorder, identified as independent contributors to h2SNP of childhood maltreatment. These 4 traits alone were sufficient to explain 58% of h2SNP of childhood maltreatment.

Conclusions

We identified putative traits that reflect h2SNP of childhood maltreatment. Elucidating the mechanisms underlying these associations may improve trauma prevention and posttraumatic intervention strategies.

Original language	English
Pages (from-to)	716-724
Number of pages	9
Journal	Biological Psychiatry: Global Open Science
Volume	3
Issue number	4
Early online date	24 Mar 2023
DOIs	https://doi.org/10.1016/j.bpsgos.2023.03.003
Publication status	Published - 6 Jun 2023

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Genetic decomposition of the_TER KUILE_2023_GOLD VoR (CC BY-NC-ND)Proof, 1.85 MBLicence: CC BY

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@article{160550d88d174b8ab7df0aca6f1b36e4,

title = "Genetic decomposition of the heritable component of reported childhood maltreatment",

abstract = "BackgroundDecades of research have shown that environmental exposures, including self-reports of trauma, are partly heritable. Heritable characteristics may influence exposure to and interpretations of environmental factors. Identifying heritable factors associated with self-reported trauma could improve our understanding of vulnerability to exposure and the interpretation of life events.MethodsWe used genome-wide association study summary statistics of childhood maltreatment, defined as reporting of abuse (emotional, sexual, and physical) and neglect (emotional and physical) (N = 185,414 participants). We calculated genetic correlations (rg) between reported childhood maltreatment and 576 traits to identify phenotypes that might explain the heritability of reported childhood maltreatment, retaining those with |rg| > 0.25. We specified multiple regression models using genomic structural equation modeling to detect residual genetic variance in childhood maltreatment after accounting for genetically correlated traits.ResultsIn 2 separate models, the shared genetic component of 12 health and behavioral traits and 7 psychiatric disorders accounted for 59% and 56% of heritability due to common genetic variants (single nucleotide polymorphism–based heritability [h2SNP]) of childhood maltreatment, respectively. Genetic influences on h2SNP of childhood maltreatment were generally accounted for by a shared genetic component across traits. The exceptions to this were general risk tolerance, subjective well-being, posttraumatic stress disorder, and autism spectrum disorder, identified as independent contributors to h2SNP of childhood maltreatment. These 4 traits alone were sufficient to explain 58% of h2SNP of childhood maltreatment.ConclusionsWe identified putative traits that reflect h2SNP of childhood maltreatment. Elucidating the mechanisms underlying these associations may improve trauma prevention and posttraumatic intervention strategies.",

author = "{ter Kuile}, Abigail and Christopher H{\"u}bel and Rosa Cheesman and Jonathan Coleman and Alicia Peel and Levey, {Daniel F} and Stein, {Murray B.} and Joel Gelernter and Christopher Rayner and Thalia Eley and Gerome Breen",

note = "Funding Information: This work was supported by the National Institute for Health and Care Research (NIHR) Biomedical Research Centre at South London and Maudsley National Health Service (NHS) Foundation Trust and King{\textquoteright}s College London and Lundbeck Foundation (Grant No. R276-2018-4581 [to CH]). The authors used the research computing facility at King{\textquoteright}s College London, Rosalind ( https://rosalind.kcl.ac.uk ), which is delivered in partnership with the NIHR Biomedical Research Centres at South London & Maudsley and Guy{\textquoteright}s & St. Thomas{\textquoteright} NHS Foundation Trusts and partly funded by capital equipment grants from the Maudsley Charity (Grant No. 980) and Guy{\textquoteright}s & St. Thomas{\textquoteright} Charity (Grant No. TR130505). The views expressed in this study are those of the authors and not necessarily those of the NHS, the NIHR, the Department of Health and Social Care, or King{\textquoteright}s College London. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising. Funding Information: This work was supported by the National Institute for Health and Care Research (NIHR) Biomedical Research Centre at South London and Maudsley National Health Service (NHS) Foundation Trust and King's College London and Lundbeck Foundation (Grant No. R276-2018-4581 [to CH]). The authors used the research computing facility at King's College London, Rosalind (https://rosalind.kcl.ac.uk), which is delivered in partnership with the NIHR Biomedical Research Centres at South London & Maudsley and Guy's & St. Thomas{\textquoteright} NHS Foundation Trusts and partly funded by capital equipment grants from the Maudsley Charity (Grant No. 980) and Guy's & St. Thomas{\textquoteright} Charity (Grant No. TR130505). The views expressed in this study are those of the authors and not necessarily those of the NHS, the NIHR, the Department of Health and Social Care, or King's College London. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising. ARtK contributed to conceptualization, formal analysis, writing of the original draft, review and editing, and visualization. CH contributed to conceptualization, formal analysis, data curation, review and editing, and visualization. RC contributed to conceptualization and review and editing. JRIC contributed to conceptualization, data curation, and review and editing. AJP contributed to conceptualization and review and editing. DFL contributed to data curation and review and editing. MBS contributed to data curation and review and editing. JG contributed to data curation and review and editing. CR contributed to formal analysis and review and editing. TCE contributed to conceptualization, writing of the original draft, review and editing, and supervision. GB contributed to conceptualization, writing of the original draft, review and editing, and supervision. We thank the participants from all cohorts who have shared their life experiences. We thank the scientists involved in the construction of all cohorts and those who provided the genetic summary results used in this study. We thank Dr. A. Grotzinger for his guidance and contribution to the interpretation of our findings using genomic multiple regression with the Genomic SEM R package. Figure 2 and Figure S1 were created with BioRender.com. Data availability of all GWAS summary statistics used for analyses can be found in Table S12 in Supplement 2. Access to Million Veteran Program PTSD GWAS summary statistics can be requested through dbGaP (phs001672.v7.p1). Analysis code can be accessed on https://github.com/abigailterkuile/reported_trauma_gsem, https://github.com/GenomicSEM/GenomicSEM/wiki, and https://github.com/bulik/ldsc/wiki/Heritability-and-Genetic-Correlation. GB has received honoraria, research or conference grants, and consulting fees from Illumina, Otsuka, and COMPASS Pathways Ltd. All other authors report no biomedical financial interests or potential conflicts of interest. Publisher Copyright: {\textcopyright} 2023 The Authors",

year = "2023",

month = jun,

day = "6",

doi = "10.1016/j.bpsgos.2023.03.003",

language = "English",

volume = "3",

pages = "716--724",

journal = "Biological Psychiatry: Global Open Science",

issn = "2667-1743",

publisher = "Elsevier",

number = "4",

}

TY - JOUR

T1 - Genetic decomposition of the heritable component of reported childhood maltreatment

AU - ter Kuile, Abigail

AU - Hübel, Christopher

AU - Cheesman, Rosa

AU - Coleman, Jonathan

AU - Peel, Alicia

AU - Levey, Daniel F

AU - Stein, Murray B.

AU - Gelernter, Joel

AU - Rayner, Christopher

AU - Eley, Thalia

AU - Breen, Gerome

N1 - Funding Information: This work was supported by the National Institute for Health and Care Research (NIHR) Biomedical Research Centre at South London and Maudsley National Health Service (NHS) Foundation Trust and King’s College London and Lundbeck Foundation (Grant No. R276-2018-4581 [to CH]). The authors used the research computing facility at King’s College London, Rosalind ( https://rosalind.kcl.ac.uk ), which is delivered in partnership with the NIHR Biomedical Research Centres at South London & Maudsley and Guy’s & St. Thomas’ NHS Foundation Trusts and partly funded by capital equipment grants from the Maudsley Charity (Grant No. 980) and Guy’s & St. Thomas’ Charity (Grant No. TR130505). The views expressed in this study are those of the authors and not necessarily those of the NHS, the NIHR, the Department of Health and Social Care, or King’s College London. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising. Funding Information: This work was supported by the National Institute for Health and Care Research (NIHR) Biomedical Research Centre at South London and Maudsley National Health Service (NHS) Foundation Trust and King's College London and Lundbeck Foundation (Grant No. R276-2018-4581 [to CH]). The authors used the research computing facility at King's College London, Rosalind (https://rosalind.kcl.ac.uk), which is delivered in partnership with the NIHR Biomedical Research Centres at South London & Maudsley and Guy's & St. Thomas’ NHS Foundation Trusts and partly funded by capital equipment grants from the Maudsley Charity (Grant No. 980) and Guy's & St. Thomas’ Charity (Grant No. TR130505). The views expressed in this study are those of the authors and not necessarily those of the NHS, the NIHR, the Department of Health and Social Care, or King's College London. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising. ARtK contributed to conceptualization, formal analysis, writing of the original draft, review and editing, and visualization. CH contributed to conceptualization, formal analysis, data curation, review and editing, and visualization. RC contributed to conceptualization and review and editing. JRIC contributed to conceptualization, data curation, and review and editing. AJP contributed to conceptualization and review and editing. DFL contributed to data curation and review and editing. MBS contributed to data curation and review and editing. JG contributed to data curation and review and editing. CR contributed to formal analysis and review and editing. TCE contributed to conceptualization, writing of the original draft, review and editing, and supervision. GB contributed to conceptualization, writing of the original draft, review and editing, and supervision. We thank the participants from all cohorts who have shared their life experiences. We thank the scientists involved in the construction of all cohorts and those who provided the genetic summary results used in this study. We thank Dr. A. Grotzinger for his guidance and contribution to the interpretation of our findings using genomic multiple regression with the Genomic SEM R package. Figure 2 and Figure S1 were created with BioRender.com. Data availability of all GWAS summary statistics used for analyses can be found in Table S12 in Supplement 2. Access to Million Veteran Program PTSD GWAS summary statistics can be requested through dbGaP (phs001672.v7.p1). Analysis code can be accessed on https://github.com/abigailterkuile/reported_trauma_gsem, https://github.com/GenomicSEM/GenomicSEM/wiki, and https://github.com/bulik/ldsc/wiki/Heritability-and-Genetic-Correlation. GB has received honoraria, research or conference grants, and consulting fees from Illumina, Otsuka, and COMPASS Pathways Ltd. All other authors report no biomedical financial interests or potential conflicts of interest. Publisher Copyright: © 2023 The Authors

PY - 2023/6/6

Y1 - 2023/6/6

N2 - BackgroundDecades of research have shown that environmental exposures, including self-reports of trauma, are partly heritable. Heritable characteristics may influence exposure to and interpretations of environmental factors. Identifying heritable factors associated with self-reported trauma could improve our understanding of vulnerability to exposure and the interpretation of life events.MethodsWe used genome-wide association study summary statistics of childhood maltreatment, defined as reporting of abuse (emotional, sexual, and physical) and neglect (emotional and physical) (N = 185,414 participants). We calculated genetic correlations (rg) between reported childhood maltreatment and 576 traits to identify phenotypes that might explain the heritability of reported childhood maltreatment, retaining those with |rg| > 0.25. We specified multiple regression models using genomic structural equation modeling to detect residual genetic variance in childhood maltreatment after accounting for genetically correlated traits.ResultsIn 2 separate models, the shared genetic component of 12 health and behavioral traits and 7 psychiatric disorders accounted for 59% and 56% of heritability due to common genetic variants (single nucleotide polymorphism–based heritability [h2SNP]) of childhood maltreatment, respectively. Genetic influences on h2SNP of childhood maltreatment were generally accounted for by a shared genetic component across traits. The exceptions to this were general risk tolerance, subjective well-being, posttraumatic stress disorder, and autism spectrum disorder, identified as independent contributors to h2SNP of childhood maltreatment. These 4 traits alone were sufficient to explain 58% of h2SNP of childhood maltreatment.ConclusionsWe identified putative traits that reflect h2SNP of childhood maltreatment. Elucidating the mechanisms underlying these associations may improve trauma prevention and posttraumatic intervention strategies.

AB - BackgroundDecades of research have shown that environmental exposures, including self-reports of trauma, are partly heritable. Heritable characteristics may influence exposure to and interpretations of environmental factors. Identifying heritable factors associated with self-reported trauma could improve our understanding of vulnerability to exposure and the interpretation of life events.MethodsWe used genome-wide association study summary statistics of childhood maltreatment, defined as reporting of abuse (emotional, sexual, and physical) and neglect (emotional and physical) (N = 185,414 participants). We calculated genetic correlations (rg) between reported childhood maltreatment and 576 traits to identify phenotypes that might explain the heritability of reported childhood maltreatment, retaining those with |rg| > 0.25. We specified multiple regression models using genomic structural equation modeling to detect residual genetic variance in childhood maltreatment after accounting for genetically correlated traits.ResultsIn 2 separate models, the shared genetic component of 12 health and behavioral traits and 7 psychiatric disorders accounted for 59% and 56% of heritability due to common genetic variants (single nucleotide polymorphism–based heritability [h2SNP]) of childhood maltreatment, respectively. Genetic influences on h2SNP of childhood maltreatment were generally accounted for by a shared genetic component across traits. The exceptions to this were general risk tolerance, subjective well-being, posttraumatic stress disorder, and autism spectrum disorder, identified as independent contributors to h2SNP of childhood maltreatment. These 4 traits alone were sufficient to explain 58% of h2SNP of childhood maltreatment.ConclusionsWe identified putative traits that reflect h2SNP of childhood maltreatment. Elucidating the mechanisms underlying these associations may improve trauma prevention and posttraumatic intervention strategies.

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U2 - 10.1016/j.bpsgos.2023.03.003

DO - 10.1016/j.bpsgos.2023.03.003

M3 - Article

SN - 2667-1743

VL - 3

SP - 716

EP - 724

JO - Biological Psychiatry: Global Open Science

JF - Biological Psychiatry: Global Open Science

IS - 4

ER -

Genetic decomposition of the heritable component of reported childhood maltreatment

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