Journal Article

International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci

Domschke, Katharina, Daskalakis, Nikolaos P., Beckham, Jean C., Khan, Alaptagin, Roy-Byrne, Peter, Nievergelt, Caroline M., Mors, Ole, Kremen, William S., Thompson, Wesley K., Seligowski, Antonia V., Norman, Sonya B., Polusny, Melissa A., Bybjerg-Grauholm, Jonas, Boks, Marco P., Panizzon, Matthew S., Rung, Ariane, Zoellner, Lori A., Almli, Lynn M., Sheerin, Christina M., Kranzler, Henry R., Smoller, Jordan W., McGlinchey, Regina E., Polimanti, Renato, Stein, Dan J., Dalvie, Shareefa, Harnal, Supriya, Uka, Aferdita Goci, Marmar, Charles, Maurer, Douglas, Stevens, Jennifer S., Risbrough, Victoria B., Maples-Keller, Jessica, Rothbaum, Alex O., Sponheim, Scott R., Zhao, Hongyu, McLean, Samuel A., Rice, John P., Bolger, Elizabeth A., Børglum, Anders D., Mortensen, Preben B., McLaughlin, Katie A., Guffanti, Guia, Forbes, David, Gordon, Scott D., Wolf, Christiane, Kimbrel, Nathan A., Amstadter, Ananda B., Wolf, Erika J., Maihofer, Adam X., Martin, Nicholas G., Jakovljevic, Miro, Winternitz, Sherry, Levey, Daniel F., Hauser, Michael A., Austin, S. Bryn, Saccone, Nancy L., Miller, Mark W., Trapido, Edward, L

2019

Overview

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5–20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson’s disease gene involved in dopamine regulation, PARK2 , is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations. Post-traumatic stress disorder (PTSD) is a common mental health problem. Here, the authors report a GWAS from the Psychiatric Genomics Consortium in which they identify two risk loci in European ancestry and one locus in African ancestry individuals and find that PTSD is genetically correlated with several other psychiatric traits.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 45 / 45/43 / 631/208/1515 / 631/208/205/2138 / 631/378/2583 / 692/699/476/1830 / Black People - genetics / Datasets as Topic / Dopamine / Ethnic factors / Female / Gene expression / Genetic diversity / Genetic Loci / Genetic Predisposition to Disease / Genome-wide association studies / Genome-Wide Association Study / Genomes / Heritability / Humanities and Social Sciences / Humans / Loci / Male / Meta-analysis / Movement disorders / multidisciplinary / Neurodegenerative diseases / Parkinson's disease / Post traumatic stress disorder / Psychological stress / Risk / Science / Science (multidisciplinary) / Sex / Sex Factors / Signs and symptoms / Single-nucleotide polymorphism / Stress Disorders, Post-Traumatic - genetics / Trauma / Ubiquitin-Protein Ligases - genetics / Veterans - statistics & numerical data / White People - genetics