Genomic influences on self-reported childhood maltreatment.

Autor: Dalvie S; SA MRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa. s.dalvie1@uct.ac.za., Maihofer AX; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.; Veterans Affairs San Diego Healthcare System, Center of Excellence for Stress and Mental Health, San Diego, CA, USA.; Veterans Affairs San Diego Healthcare System, Research Service, San Diego, CA, USA., Coleman JRI; King's College London, Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, London, UK.; King's College London, NIHR BRC at the Maudsley, London, UK., Bradley B; Atlanta VA Health Care System, Mental Health Service Line, Decatur, GA, USA.; Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, USA., Breen G; King's College London, Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, London, UK.; King's College London, NIHR BRC at the Maudsley, London, UK., Brick LA; Alpert Medical School of Brown University, Providence, RI, USA., Chen CY; Massachusetts General Hospital, Analytic and Translational Genetics Unit, Boston, MA, USA.; Massachusetts General Hospital, Psychiatric and Neurodevelopmental Genetics Unit (PNGU), Boston, MA, USA.; Broad Institute of MIT and Harvard, Stanley Center for Psychiatric Research, Cambridge, MA, USA., Choi KW; Broad Institute of MIT and Harvard, Stanley Center for Psychiatric Research, Cambridge, MA, USA.; Harvard T.H. Chan School of Public Health, Department of Epidemiology, Boston, MA, USA.; Massachusetts General Hospital, Department of Psychiatry, Boston, MA, USA., Duncan LE; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA., Guffanti G; Harvard Medical School, Department of Psychiatry, Boston, MA, USA.; McLean Hospital, Belmont, MA, USA., Haas M; Cohen Veterans Bioscience, Cambridge, MA, USA., Harnal S; Broad Institute of MIT and Harvard, Stanley Center for Psychiatric Research, Cambridge, MA, USA., Liberzon I; Department of Psychiatry, University of Michigan Medical School, Ann Arbor, MI, USA., Nugent NR; Alpert Medical School of Brown University, Providence, RI, USA.; Bradley/Hasbro Children's Research Center of Rhode Island Hospital, Providence, RI, USA., Provost AC; Cohen Veterans Bioscience, Cambridge, MA, USA., Ressler KJ; Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, USA.; Harvard Medical School, Department of Psychiatry, Boston, MA, USA.; McLean Hospital, Belmont, MA, USA., Torres K; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.; Veterans Affairs San Diego Healthcare System, Center of Excellence for Stress and Mental Health, San Diego, CA, USA.; Veterans Affairs San Diego Healthcare System, Research Service, San Diego, CA, USA., Amstadter AB; Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Richmond, VA, USA., Bryn Austin S; Harvard Medical School, Department of Psychiatry, Boston, MA, USA.; Harvard School of Public Health, Department of Social and Behavioral Sciences, Boston, MA, USA.; Boston Children's Hospital, Division of Adolescent and Young Adult Medicine, Boston, MA, USA.; Brigham and Women's Hospital, Channing Division of Network Medicine, Boston, MA, USA., Baker DG; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.; Veterans Affairs San Diego Healthcare System, Center of Excellence for Stress and Mental Health, San Diego, CA, USA.; Veterans Affairs San Diego Healthcare System, Psychiatry Service, San Diego, CA, USA., Bolger EA; Harvard Medical School, Department of Psychiatry, Boston, MA, USA.; McLean Hospital, Belmont, MA, USA., Bryant RA; Department of Psychology, University of New South Wales, Sydney, NSW, Australia., Calabrese JR; Department of Psychiatry, University Hospitals, Cleveland, OH, USA., Delahanty DL; Department of Psychological Sciences, Kent State University, Kent, OH, USA.; Research and Sponsored Programs, Kent State University, Kent, OH, USA., Farrer LA; Department of Medicine, Boston University School of Medicine, Boston, MA, USA., Feeny NC; Department of Psychological Sciences, Case Western Reserve University, Cleveland, OH, USA., Flory JD; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Forbes D; Department of Psychiatry, University of Melbourne, Melbourne, VIC, Australia., Galea S; Department of Psychological and Brain Sciences, Boston University, Boston, MA, USA., Gautam A; US Army Medical Research and Materiel Command, Fort Detrick, MD, USA., Gelernter J; US Department of Veterans Affairs, Department of Psychiatry, West Haven, CT, USA.; VA Connecticut Healthcare Center, West Haven, CT, USA.; Department of Genetics and Neuroscience, Yale University School of Medicine, New Haven, CT, USA., Hammamieh R; US Army Medical Research and Materiel Command, USACEHR, Fort Detrick, MD, USA., Jett M; US Army Medical Research and Materiel Command, USACEHR, Fort Detrick, MD, USA., Junglen AG; Department of Psychological Sciences, Kent State University, Kent, OH, USA., Kaufman ML; Harvard Medical School, Department of Psychiatry, Boston, MA, USA.; McLean Hospital, Belmont, MA, USA., Kessler RC; Harvard Medical School, Department of Health Care Policy, Boston, MA, USA., Khan A; McLean Hospital, Belmont, MA, USA.; Harvard Medical School, Department of Health Care Policy, Boston, MA, USA., Kranzler HR; Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.; Mental Illness Research, Education and Clinical Center, Crescenz VAMC, Philadelphia, PA, USA., Lebois LAM; Harvard Medical School, Department of Psychiatry, Boston, MA, USA.; McLean Hospital, Belmont, MA, USA., Marmar C; Department of Psychiatry, New York University School of Medicine, New York, NY, USA., Mavissakalian MR; Department of Psychiatry, University Hospitals, Cleveland, OH, USA., McFarlane A; University of Adelaide, Centre for Traumatic Stress Studies, Adelaide, SA, Australia., Donnell MO; Department of Psychiatry, University of Melbourne, Melbourne, VIC, Australia., Orcutt HK; Department of Psychology, Northern Illinois University, DeKalb, IL, USA., Pietrzak RH; U.S. Department of Veterans Affairs National Center for Posttraumatic Stress Disorder, West Haven, CT, USA.; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA., Risbrough VB; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.; Veterans Affairs San Diego Healthcare System, Center of Excellence for Stress and Mental Health, San Diego, CA, USA.; Veterans Affairs San Diego Healthcare System, Research Service, San Diego, CA, USA., Roberts AL; Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA., Rothbaum AO; Department of Psychological Sciences, Case Western Reserve University, Cleveland, OH, USA., Roy-Byrne P; Department of Psychiatry, University of Washington, Seattle, WA, USA., Ruggiero K; Department of Nursing and Department of Psychiatry, Medical University of South Carolina, Charleston, SC, USA., Seligowski AV; Harvard Medical School, Department of Psychiatry, Boston, MA, USA.; McLean Hospital, Belmont, MA, USA., Sheerin CM; Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Richmond, VA, USA., Silove D; Department of Psychiatry, University of New South Wales, Sydney, NSW, Australia., Smoller JW; 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.; Massachusetts General Hospital, Department of Psychiatry, Boston, MA, USA., Stein MB; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.; Veterans Affairs San Diego Healthcare System, Psychiatry Service, San Diego, CA, USA.; Veterans Affairs San Diego Healthcare System, Million Veteran Program, San Diego, CA, USA., Teicher MH; Harvard Medical School, Department of Psychiatry, Boston, MA, USA.; McLean Hospital, Belmont, MA, USA., Ursano RJ; Department of Psychiatry, Uniformed Services University, Bethesda, MD, USA., Van Hooff M; University of Adelaide, Centre for Traumatic Stress Studies, Adelaide, SA, Australia., Winternitz S; Harvard Medical School, Department of Psychiatry, Boston, MA, USA.; McLean Hospital, Belmont, MA, USA., Wolff JD; McLean Hospital, Belmont, MA, USA., Yehuda R; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Department of Mental Health, James J. Peters VA Medical Center, Bronx, NY, USA., Zhao H; Department of Biostatistics, Yale University, New Haven, CT, USA., Zoellner LA; Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA., Stein DJ; SA MRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa., Koenen KC; Massachusetts General Hospital, Psychiatric and Neurodevelopmental Genetics Unit (PNGU), Boston, MA, USA.; Broad Institute of MIT and Harvard, Stanley Center for Psychiatric Research, Cambridge, MA, USA.; Harvard School of Public Health, Department of Epidemiology, Boston, MA, USA., Nievergelt CM; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.; Veterans Affairs San Diego Healthcare System, Center of Excellence for Stress and Mental Health, San Diego, CA, USA.; Veterans Affairs San Diego Healthcare System, Research Service, San Diego, CA, USA.
Jazyk: angličtina
Zdroj: Translational psychiatry [Transl Psychiatry] 2020 Jan 27; Vol. 10 (1), pp. 38. Date of Electronic Publication: 2020 Jan 27.
DOI: 10.1038/s41398-020-0706-0
Abstrakt: 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 2 snp ), (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 2 snp 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 -8 , FOXP1; rs10262462, p = 3.24 × 10 -8 , FOXP2) were identified in the discovery dataset but were not replicated in PGC-PTSD. h 2 snp for childhood maltreatment was ~6% and the PRS derived from the UKBB was significantly predictive of childhood maltreatment in PGC-PTSD (r 2  = 0.0025; p = 1.8 × 10 -15 ). The most significant genetic correlation of childhood maltreatment was with depressive symptoms (r g  = 0.70, p = 4.65 × 10 -40 ), 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.
Databáze: MEDLINE