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

Abstract

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.

Type

Journal article

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1038/s41467-019-12576-w

Publication Info

Nievergelt, Caroline M, Adam X Maihofer, Torsten Klengel, Elizabeth G Atkinson, Chia-Yen Chen, Karmel W Choi, Jonathan RI Coleman, Shareefa Dalvie, et al. (2019). International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci. Nature communications, 10(1). p. 4558. 10.1038/s41467-019-12576-w Retrieved from https://hdl.handle.net/10161/29327.

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Scholars@Duke

Ashley-Koch

Allison Elizabeth Ashley-Koch

Professor in Medicine

My work focuses on the dissection of human traits using multi-omic technologies (genetics, epigenetics, metabolomics and proteomics).  I am investigating the basis of several neurological and psychiatric conditions such as neural tube defects and post-traumatic stress disorder. I also study modifiers of sickle cell disease.

Beckham

Jean Crowell Beckham

Professor in Psychiatry and Behavioral Sciences

Interest in assessment and treatment of trauma, particularly as occurs for both women and men during military service; focus in treatment outcome of differential and collective contribution for psychopharmacological and behavioral interventions in PTSD populations; long term physical health effects of chronic posttraumatic stress disorder.

Hauser

Michael Arthur Hauser

Professor in Medicine

Dr. Hauser has a strong interest in ocular genetics. Genomic studies at the Center for Human Genetics have identified multiple linkage peaks and susceptibility genes in primary open angle glaucoma (POAG) and age related macular degeneration (AMD). Dr. Hauser has recently accepted a 20% appointment at the Singapore Eye Research INstitute and the Duke/National University of Singapore.  In collaboration with multiple collaborators in Singapore, and Dr. Rand Allingham at the Duke Eye Center, Dr. Hauser is currently conducting a genome wide association study for glaucoma in individuals of African ancestry. These investigations include large datasets collected in Ghana, Nigeria, and South Africa.  
 
Dr. Hauser is also involved in collaborative investigations into the genetics of post-tramatic stress disorder in US veterans from Iraq and Afghanistan.   Major collaborators include Dr. Allison Ashley Koch, Dr. Jean Beckham, Dr. Christine Marx and the MIRECC Collaborative group at the Durham Veteran's Administration.  We have published a genome wide association study, as well as numerous investigations into candidate genes.  Epigenomic DNA methylation analysis and gene expression analysis of 3500 individuals is currently ongoing. 


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