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

CM Nievergelt; AX Maihofer; T Klengel; EG Atkinson; CY Chen; KW Choi; JRI Coleman; S Dalvie; LE Duncan; J Gelernter; DF Levey; MW Logue; R Polimanti; AC Provost; A Ratanatharathorn; MB Stein; K Torres; AE Aiello; LM Almli; AB Amstadter; SB Andersen; OA Andreassen; PA Arbisi; AE Ashley-Koch; SB Austin; E Avdibegovic; D Babić; M Bækvad-Hansen; DG Baker; JC Beckham; LJ Bierut; JI Bisson; MP Boks; EA Bolger; AD Børglum; B Bradley; M Brashear; G Breen; RA Bryant; AC Bustamante; J Bybjerg-Grauholm; JR Calabrese; JM Caldas- de- Almeida; AM Dale; MJ Daly; NP Daskalakis; J Deckert; DL Delahanty; MF Dennis; SG Disner; K Domschke; A Dzubur-Kulenovic; CR Erbes; A Evans; LA Farrer; NC Feeny; JD Flory; D Forbes; CE Franz; S Galea; ME Garrett; B Gelaye; E Geuze; C Gillespie; AG Uka; SD Gordon; G Guffanti; R Hammamieh; S Harnal; MA Hauser; AC Heath; SMJ Hemmings; DM Hougaard; M Jakovljevic; M Jett; EO Johnson; I Jones; T Jovanovic; XJ Qin; AG Junglen; KI Karstoft; ML Kaufman; RC Kessler; A Khan; NA Kimbrel; AP King; N Koen; HR Kranzler; WS Kremen; BR Lawford; LAM Lebois; CE Lewis; SD Linnstaedt; A Lori; B Lugonja; JJ Luykx; MJ Lyons; J Maples-Keller; C Marmar; AR Martin

Journal article

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

CM Nievergelt, AX Maihofer, T Klengel, EG Atkinson, CY Chen, KW Choi, JRI Coleman, S Dalvie, LE Duncan, J Gelernter, DF Levey, MW Logue, R Polimanti, AC Provost, A Ratanatharathorn, MB Stein, K Torres, AE Aiello, LM Almli, AB Amstadter Show all

Nature Communications | NATURE PORTFOLIO | Published : 2019

DOI: 10.1038/s41467-019-12576-w

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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..

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University of Melbourne Researchers

David Forbes Author

Meaghan O'Donnell Author

Grants

Awarded by National Institute of Mental Health

Funding Acknowledgements

This work was funded by Cohen Veterans Bioscience, the NIMH/U.S. Army Medical Research and Materiel Command Grant R01MH106595 to C.M.N., I.L., K.J.R. and K.C.K., One Mind, and supported by 5U01MH109539 to the Psychiatric Genomics Consortium. Statistical Analysis were carried out on the NL Genetic Cluster computer (URL) hosted by SURFsara. Genotyping of samples was supported in part through the Stanley Center for Psychiatric Genetics at the Broad Institute of MIT and Harvard. This research has been conducted using the UK biobank resource under application number 16577. This work would not have been possible without the contributions of the investigators who comprise the PGC-PTSD working group, and especially the more than 206,000 research participants worldwide who shared their life experiences and biological samples with PGC-PTSD investigators. Full acknowledgements are in the Supplementary Note 2.