Genomic influences on self-reported childhood maltreatment.
Journal: Translational psychiatry
Volume: 10
Issue: 1
Year of Publication: 2021
Affiliated Institutions:
SA MRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa. s.dalvie@uct.ac.za.
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
King's College London, Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, London, UK.
Atlanta VA Health Care System, Mental Health Service Line, Decatur, GA, USA.
Alpert Medical School of Brown University, Providence, RI, USA.
Massachusetts General Hospital, Analytic and Translational Genetics Unit, Boston, MA, USA.
Broad Institute of MIT and Harvard, Stanley Center for Psychiatric Research, Cambridge, MA, USA.
Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
Harvard Medical School, Department of Psychiatry, Boston, MA, USA.
Cohen Veterans Bioscience, Cambridge, MA, USA.
Department of Psychiatry, University of Michigan Medical School, Ann Arbor, MI, USA.
Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, USA.
Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Richmond, VA, USA.
Department of Psychology, University of New South Wales, Sydney, NSW, Australia.
Department of Psychiatry, University Hospitals, Cleveland, OH, USA.
Department of Psychological Sciences, Kent State University, Kent, OH, USA.
Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
Department of Psychological Sciences, Case Western Reserve University, Cleveland, OH, USA.
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Psychiatry, University of Melbourne, Melbourne, VIC, Australia.
Department of Psychological and Brain Sciences, Boston University, Boston, MA, USA.
US Army Medical Research and Materiel Command, Fort Detrick, MD, USA.
US Department of Veterans Affairs, Department of Psychiatry, West Haven, CT, USA.
US Army Medical Research and Materiel Command, USACEHR, Fort Detrick, MD, USA.
Harvard Medical School, Department of Health Care Policy, Boston, MA, USA.
McLean Hospital, Belmont, MA, USA.
Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Department of Psychiatry, New York University School of Medicine, New York, NY, USA.
University of Adelaide, Centre for Traumatic Stress Studies, Adelaide, SA, Australia.
Department of Psychology, Northern Illinois University, DeKalb, IL, USA.
U.S. Department of Veterans Affairs National Center for Posttraumatic Stress Disorder, West Haven, CT, USA.
Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Department of Psychiatry, University of Washington, Seattle, WA, USA.
Department of Nursing and Department of Psychiatry, Medical University of South Carolina, Charleston, SC, USA.
Department of Psychiatry, University of New South Wales, Sydney, NSW, Australia.
Department of Psychiatry, Uniformed Services University, Bethesda, MD, USA.
Department of Biostatistics, Yale University, New Haven, CT, USA.
Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA.
SA MRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.
Massachusetts General Hospital, Psychiatric and Neurodevelopmental Genetics Unit (PNGU), Boston, MA, USA.
Abstract summary
Childhood maltreatment is highly prevalent and serves as a risk factor for mental and physical disorders. Self-reported childhood maltreatment appears heritable, but the specific genetic influences on this phenotype are largely unknown. The aims of this study were to (1) identify genetic variation associated with self-reported childhood maltreatment, (2) estimate SNP-based heritability (h), (3) assess predictive value of polygenic risk scores (PRS) for childhood maltreatment, and (4) quantify genetic overlap of childhood maltreatment with mental and physical health-related phenotypes, and condition the top hits from our analyses when such overlap is present. Genome-wide association analysis for childhood maltreatment was undertaken, using a discovery sample from the UK Biobank (UKBB) (n = 124,000) and a replication sample from the Psychiatric Genomics Consortium-posttraumatic stress disorder group (PGC-PTSD) (n = 26,290). h for childhood maltreatment and genetic correlations with mental/physical health traits were calculated using linkage disequilibrium score regression. PRS was calculated using PRSice and mtCOJO was used to perform conditional analysis. Two genome-wide significant loci associated with childhood maltreatment (rs142346759, p = 4.35 × 10, FOXP1; rs10262462, p = 3.24 × 10, FOXP2) were identified in the discovery dataset but were not replicated in PGC-PTSD. h for childhood maltreatment was ~6% and the PRS derived from the UKBB was significantly predictive of childhood maltreatment in PGC-PTSD (r = 0.0025; p = 1.8 × 10). The most significant genetic correlation of childhood maltreatment was with depressive symptoms (r = 0.70, p = 4.65 × 10), although we show evidence that our top hits may be specific to childhood maltreatment. This is the first large-scale genetic study to identify specific variants associated with self-reported childhood maltreatment. Speculatively, FOXP genes might influence externalizing traits and so be relevant to childhood maltreatment. Alternatively, these variants may be associated with a greater likelihood of reporting maltreatment. A clearer understanding of the genetic relationships of childhood maltreatment, including particular abuse subtypes, with a range of phenotypes, may ultimately be useful in in developing targeted treatment and prevention strategies.
Authors & Co-authors:
Dalvie Shareefa S
Maihofer Adam X AX
Coleman Jonathan R I JRI
Bradley Bekh B
Breen Gerome G
Brick Leslie A LA
Chen Chia-Yen CY
Choi Karmel W KW
Duncan Laramie E LE
Guffanti Guia G
Haas Magali M
Harnal Supriya S
Liberzon Israel I
Nugent Nicole R NR
Provost Allison C AC
Ressler Kerry J KJ
Torres Katy K
Amstadter Ananda B AB
Bryn Austin S S
Baker Dewleen G DG
Bolger Elizabeth A EA
Bryant Richard A RA
Calabrese Joseph R JR
Delahanty Douglas L DL
Farrer Lindsay A LA
Feeny Norah C NC
Flory Janine D JD
Forbes David D
Galea Sandro S
Gautam Aarti A
Gelernter Joel J
Hammamieh Rasha R
Jett Marti M
Junglen Angela G AG
Kaufman Milissa L ML
Kessler Ronald C RC
Khan Alaptagin A
Kranzler Henry R HR
Lebois Lauren A M LAM
Marmar Charles C
Mavissakalian Matig R MR
McFarlane Alexander A
Donnell Meaghan O' MO
Orcutt Holly K HK
Pietrzak Robert H RH
Risbrough Victoria B VB
Roberts Andrea L AL
Rothbaum Alex O AO
Roy-Byrne Peter P
Ruggiero Ken K
Seligowski Antonia V AV
Sheerin Christina M CM
Silove Derrick D
Smoller Jordan W JW
Stein Murray B MB
Teicher Martin H MH
Ursano Robert J RJ
Van Hooff Miranda M
Winternitz Sherry S
Wolff Jonathan D JD
Yehuda Rachel R
Zhao Hongyu H
Zoellner Lori A LA
Stein Dan J DJ
Koenen Karestan C KC
Nievergelt Caroline M CM
Study Outcome
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