Enhancing Discovery of Genetic Variants for Posttraumatic Stress Disorder Through Integration of Quantitative Phenotypes and Trauma Exposure Information.

Autor:	Maihofer AX; Department of Psychiatry, University of California San Diego, La Jolla, California; Department of Family Medicine and Public Health, University of California San Diego, La Jolla, California; Center of Excellence for Stress and Mental Health, Veterans Affairs Healthcare System, San Diego, California. Electronic address: amaihofer@health.ucsd.edu., Choi KW; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts., Coleman JRI; Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom; National Institute of Health Research Maudsley Biomedical Research Centre, King's College London, London, United Kingdom., Daskalakis NP; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts; Center of Excellence in Depression and Anxiety Disorders, Belmont, Massachusetts., Denckla CA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts., Ketema E; Department of Psychiatry, University of California San Diego, La Jolla, California; Center of Excellence for Stress and Mental Health, Veterans Affairs Healthcare System, San Diego, California; Research Service, Veterans Affairs Healthcare System, San Diego, California., Morey RA; Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, North Carolina., Polimanti R; Department of Psychiatry, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut; Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut., Ratanatharathorn A; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Department of Epidemiology, Columbia University Mailman School of Public Health, New York., Torres K; Department of Psychiatry, University of California San Diego, La Jolla, California; Center of Excellence for Stress and Mental Health, Veterans Affairs Healthcare System, San Diego, California; Research Service, Veterans Affairs Healthcare System, San Diego, California., Wingo AP; Division of Mental Health, Atlanta Veterans Affairs Medical Center, Decatur, Georgia; Departments of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia., Zai CC; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts; Tanenbaum Centre for Pharmacogenetics, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Molecular Brain Science, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Department of Laboratory Medicine and Pathology, University of Toronto, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada., Aiello AE; Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina., Almli LM; Departments of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia., Amstadter AB; Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Richmond, Virginia., Andersen SB; Research and Knowledge Centre, The Danish Veteran Centre, Ringsted, Denmark., Andreassen OA; Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; Norwegian Centre for Mental Disorders Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Arbisi PA; Mental Health Service, Minneapolis Veterans Affairs Health Care System, Minneapolis, Minnesota; Department of Psychiatry and Behavioral Sciences, Medical School, University of Minnesota, Minneapolis, Minnesota., Ashley-Koch AE; Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, North Carolina., Austin SB; Department of Social and Behavioral Sciences, Harvard T.H. 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Center of Mental Health, Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Würzburg, Germany., Delahanty DL; Department of Psychological Sciences, Kent State University, Kent, Ohio; Research and Sponsored Programs, Kent State University, Kent, Ohio., Dennis MF; Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, North Carolina; Research Service, Durham Veterans Affairs Medical Center, Durham, North Carolina; Genetics Research Laboratory, Veterans Affairs Mid-Atlantic Mental Illness Research, Education, and Clinical Center, Durham, North Carolina., Disner SG; Research Service Line, Minneapolis Veterans Affairs Health Care System, Minneapolis, Minnesota., Domschke K; Department of Psychiatry and Psychotherapy, Faculty of Medicine, University Medical Center Freiburg, Freiburg, Germany; Centre for Basics in Neuromodulation, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Duncan LE; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California., Džubur Kulenović A; 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Jazyk:	angličtina
Zdroj:	Biological psychiatry [Biol Psychiatry] 2022 Apr 01; Vol. 91 (7), pp. 626-636. Date of Electronic Publication: 2021 Sep 28.
DOI:	10.1016/j.biopsych.2021.09.020
Abstrakt:	Background: Posttraumatic stress disorder (PTSD) is heritable and a potential consequence of exposure to traumatic stress. Evidence suggests that a quantitative approach to PTSD phenotype measurement and incorporation of lifetime trauma exposure (LTE) information could enhance the discovery power of PTSD genome-wide association studies (GWASs). Methods: A GWAS on PTSD symptoms was performed in 51 cohorts followed by a fixed-effects meta-analysis (N = 182,199 European ancestry participants). A GWAS of LTE burden was performed in the UK Biobank cohort (N = 132,988). Genetic correlations were evaluated with linkage disequilibrium score regression. Multivariate analysis was performed using Multi-Trait Analysis of GWAS. Functional mapping and annotation of leading loci was performed with FUMA. Replication was evaluated using the Million Veteran Program GWAS of PTSD total symptoms. Results: GWASs of PTSD symptoms and LTE burden identified 5 and 6 independent genome-wide significant loci, respectively. There was a 72% genetic correlation between PTSD and LTE. PTSD and LTE showed largely similar patterns of genetic correlation with other traits, albeit with some distinctions. Adjusting PTSD for LTE reduced PTSD heritability by 31%. Multivariate analysis of PTSD and LTE increased the effective sample size of the PTSD GWAS by 20% and identified 4 additional loci. Four of these 9 PTSD loci were independently replicated in the Million Veteran Program. Conclusions: Through using a quantitative trait measure of PTSD, we identified novel risk loci not previously identified using prior case-control analyses. PTSD and LTE have a high genetic overlap that can be leveraged to increase discovery power through multivariate methods. (Copyright © 2021 Society of Biological Psychiatry. All rights reserved.)
Databáze:	MEDLINE
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