Largest GWAS of PTSD (N=20 070) yields genetic overlap with schizophrenia and sex differences in heritability.

Journal: Molecular psychiatry

Volume: 23

Issue: 3

Year of Publication: 2019

Affiliated Institutions:  Department of Psychiatry, Stanford University, Stanford, CA, USA. Department of Epidemiology, Columbia University, New York, NY, USA. Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, Chapel Hill, NC, USA. Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, USA. Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA. Department of Medicine, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USA. Veterans Affairs San Diego Healthcare System and Veterans Affairs Center of Excellence for Stress and Mental Health, San Diego, CA, USA. Veterans Affairs Durham Healthcare System, Durham, NC, USA. Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA. Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK. Atlanta VA Medical Center, Atlanta, GA, USA. The Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA. Division of Human Genetics, University of Cape Town, Cape Town, South Africa. Biomedical Genetics, Boston University School of Medicine, Boston, MA, USA. Boston University School of Public Health, Boston, MA, USA. Department of Psychiatry, Yale University School of Medicine and VA CT Healthcare System, New Haven, CT, USA. Department of Psychiatry, Harvard University, Cambridge, MA, USA. RTI International, Research Triangle Park, NC, USA. Department of Health Care Policy, Harvard Medical School, Boston, MA, USA. Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA. Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa. Department of Psychiatry, University of Pennsylvania Perelman School of Medicine and VISN MIRECC, Crescenz VAMC, Philadelphia, PA, USA. VA Boston Healthcare System, Jamaica Plain, MA, USA. Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA. Broad Institute of MIT and Harvard, Stanley Center for Psychiatric Research, Boston, MA, USA. Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA. Division of Behavioral Genetics, Department of Psychiatry, Rhode Island Hospital, Providence, RI, USA. Department of Psychiatry, Washington University, St Louis, MO, USA. Department of Social and Behavioral Sciences, Harvard T. H. Chan School of Public Health Cambridge, MA, USA. Department of Genetics, Washington University, St Louis, MO, USA. Center for Cardiovascular Behavioral Health, Columbia University Medical Center, New York, NY, USA. Department of Psychology and Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA. Center for the Study of Traumatic Stress, Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. Department of Molecular & Integrative Physiology and Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA. James J. Peters Bronx Veterans Affairs and Department of Psychiatry, Icahn School of Medicine at Mount Sinai, Bronx, NY, USA. Department of Biostatistics, Yale University, New Haven, CT, USA.

Abstract summary 

The Psychiatric Genomics Consortium-Posttraumatic Stress Disorder group (PGC-PTSD) combined genome-wide case-control molecular genetic data across 11 multiethnic studies to quantify PTSD heritability, to examine potential shared genetic risk with schizophrenia, bipolar disorder, and major depressive disorder and to identify risk loci for PTSD. Examining 20 730 individuals, we report a molecular genetics-based heritability estimate (h) for European-American females of 29% that is similar to h for schizophrenia and is substantially higher than h in European-American males (estimate not distinguishable from zero). We found strong evidence of overlapping genetic risk between PTSD and schizophrenia along with more modest evidence of overlap with bipolar and major depressive disorder. No single-nucleotide polymorphisms (SNPs) exceeded genome-wide significance in the transethnic (overall) meta-analysis and we do not replicate previously reported associations. Still, SNP-level summary statistics made available here afford the best-available molecular genetic index of PTSD-for both European- and African-American individuals-and can be used in polygenic risk prediction and genetic correlation studies of diverse phenotypes. Publication of summary statistics for ∼10 000 African Americans contributes to the broader goal of increased ancestral diversity in genomic data resources. In sum, the results demonstrate genetic influences on the development of PTSD, identify shared genetic risk between PTSD and other psychiatric disorders and highlight the importance of multiethnic/racial samples. As has been the case with schizophrenia and other complex genetic disorders, larger sample sizes are needed to identify specific risk loci.

Authors & Co-authors:  Duncan L E LE Ratanatharathorn A A Aiello A E AE Almli L M LM Amstadter A B AB Ashley-Koch A E AE Baker D G DG Beckham J C JC Bierut L J LJ Bisson J J Bradley B B Chen C-Y CY Dalvie S S Farrer L A LA Galea S S Garrett M E ME Gelernter J E JE Guffanti G G Hauser M A MA Johnson E O EO Kessler R C RC Kimbrel N A NA King A A Koen N N Kranzler H R HR Logue M W MW Maihofer A X AX Martin A R AR Miller M W MW Morey R A RA Nugent N R NR Rice J P JP Ripke S S Roberts A L AL Saccone N L NL Smoller J W JW Stein D J DJ Stein M B MB Sumner J A JA Uddin M M Ursano R J RJ Wildman D E DE Yehuda R R Zhao H H Daly M J MJ Liberzon I I Ressler K J KJ Nievergelt C M CM Koenen K C KC

Study Outcome 

Source Link: Visit source

Statistics
Citations :  Kessler RC, Demler O, Frank RG, Olfson M, Pincus HA, Walters EE et al. Prevalence and treatment of mental disorders, 1990 to 2003. N Engl J Med 2005; 352: 2515–2523.
Authors :  49
Identifiers
Doi : 10.1038/mp.2017.77
SSN : 1476-5578
Study Population
Males,Females
Mesh Terms
Adult
Other Terms
Study Design
Case Study,Cross Sectional Study
Study Approach
Country of Study
Publication Country
England