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

• Type of Material: Article
• Authors: LE Duncan, Stanford University; A Ratanatharathorn, Columbia University; AE Aiello, University of North Carolina; Lynn Almli, Emory University; AB Amstadter, Virginia Commonwealth University; AE Ashley-Koch, Duke University; DG Baker, Veterans Affairs San Diego Healthcare Syst; JC Beckham, Veterans Affairs Durham Healthcare System; LJ Bierut, Washington University; J Bisson, Cardiff University; Bekh Bradley-Davino, Emory University; C-Y Chen, Massachusetts General Hospital; S Dalvie, University of Cape Town; LA Farrer, Boston University; S Galea, Boston University; ME Garrett, Duke University; JE Gelernter, Yale University; G Guffanti, Harvard University; MA Hauser, Duke University; EO Johnson, RTI International; RC Kessler, Harvard Medical School; NA Kimbrel, Veterans Affairs Durham Healthcare System; A King, University of Michigan; N Koen, University of Cape Town; HR Kranzler, University of Pennsylvania; MW Logue, VA Boston Healthcare Syst; AX Maihofer, University of California San Diego; AR Martin, Broad Inst MIT & Harvard; MW Miller, VA Boston Healthcare System; RA Morey, Duke University; NR Nugent, Rhode Island Hospital; JP Rice, Washington University; S Ripke, Broad Institute of MIT and Harvard; AL Roberts, Harvard T. H. Chan School of Public Health; NL Saccone, Washington University; JW Smoller, Broad Institute of MIT and Harvard; DJ Stein, University of Cape Town; MB Stein, University of California, San Diego; JA Sumner, Columbia University; M Uddin, University of Illinois at Urbana-Champaign; RJ Ursano, Uniformed Services University of the Health Sciences; DE Wildman, University of Illinois at Urbana-Champaign; R Yehuda, Icahn School of Medicine at Mount Sinai; H Zhao, Yale University; MJ Daly, Broad Institute of MIT and Harvard; I Liberzon, University of Michigan; Kerry Ressler, Emory University; CM Nievergelt, Veterans Affairs San Diego Healthcare Syst; KC Koenen, Broad Institute of MIT and Harvard
• Language: English
• Date: 2018-03-01
• Publisher: Nature Publishing Group: Open Access Hybrid Model Option B
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2018.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/mp.2017.77
• Title of Journal or Parent Work: Molecular Psychiatry
• ISSN: 1359-4184
• Volume: 23
• Issue: 3
• Start Page: 666
• End Page: 673
• Grant/Funding Information: Analysis and other work on this project was supported by 3U01MH094432-03S1 (MJD) and 5U01MH094432-04 (MJD).; We thank One Mind (LED), Cohen Veterans Bioscience (LED and PGC-PTSD group) and the Stanley Center for Psychiatric Research for their financial support.
• Keywords: Neurosciences; Life Sciences & Biomedicine; GENOME-WIDE ASSOCIATION; POSTTRAUMATIC-STRESS-DISORDER; BIRTH COHORT; MENTAL-DISORDERS; GENDER-DIFFERENCES; Science & Technology; HUMAN HEIGHT; Psychiatry; SUSCEPTIBILITY LOCI; TRAUMA; VULNERABILITY; Biochemistry & Molecular Biology; Neurosciences & Neurology; MAJOR DEPRESSION
• Research Categories: Engineering, Biomedical; Biology, Molecular; Biology, Neuroscience

Abstract

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 2 SNP) for European-American females of 29% that is similar to h 2 SNP for schizophrenia and is substantially higher than h 2 SNP 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 1/410 000 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.