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

Nievergelt, C.M.; Maihofer, A.X.; Klengel, T.; Atkinson, E.G.; Chen, C.Y.; Choi, K.W.; ... ; Koenen, K.C. (2019)

Article / Letter to editor

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.

• All authors: Nievergelt, C.M.; Maihofer, A.X.; Klengel, T.; Atkinson, E.G.; Chen, C.Y.; Choi, K.W.; Coleman, J.R.I.; Dalvie, S.; Duncan, L.E.; Gelernter, J.; Levey, D.F.; Logue, M.W.; Polimanti, R.; Provost, A.C.; Ratanatharathorn, A.; Stein, M.B.; Torres, K.; Aiello, A.E.; Almli, L.M.; Amstadter, A.B.; Andersen, S.B.; Andreassen, O.A.; Arbisi, P.A.; Ashley-Koch, A.E.; Austin, S.B.; Avdibegovic, E.; Babic, D.; Baekvad-Hansen, M.; Baker, D.G.; Beckham, J.C.; Bierut, L.J.; Bisson, J.I.; Boks, M.P.; Bolger, E.A.; Brglum, A.D.; Bradley, B.; Brashear, M.; Breen, G.; Bryant, R.A.; Bustamante, A.C.; Bybjerg-Grauholm, J.; Calabrese, J.R.; Caldas-de-Almeida, J.M.; Dale, A.M.; Daly, M.J.; Daskalakis, N.P.; Deckert, J.; Delahanty, D.L.; Dennis, M.F.; Disner, S.G.; Domschke, K.; Dzubur-Kulenovic, A.; Erbes, C.R.; Evans, A.; Farrer, L.A.; Feeny, N.C.; Flory, J.D.; Forbes, D.; Franz, C.E.; Galea, S.; Garrett, M.E.; Gelaye, B.; Geuze, E.; Gillespie, C.; Uka, A.G.; Gordon, S.D.; Guffanti, G.; Hammamieh, R.; Harnal, S.; Hauser, M.A.; Heath, A.C.; Hemmings, S.M.J.; Hougaard, D.M.; Jakovljevic, M.; Jett, M.; Johnson, E.O.; Jones, I.; Jovanovic, T.; Qin, X.J.; Junglen, A.G.; Karstoft, K.I.; Kaufman, M.L.; Kessler, R.C.; Khan, A.; Kimbrel, N.A.; King, A.P.; Koen, N.; Kranzler, H.R.; Kremen, W.S.; Lawford, B.R.; Lebois, L.A.M.; Lewis, C.E.; Linnstaedt, S.D.; Lori, A.; Lugonja, B.; Luykx, J.J.; Lyons, M.J.; Maples-Keller, J.; Marmar, C.; Martin, A.R.; Martin, N.G.; Maurer, D.; Mavissakalian, M.R.; McFarlane, A.; McGlinchey, R.E.; McLaughlin, K.A.; McLean, S.A.; McLeay, S.; Mehta, D.; Milberg, W.P.; Miller, M.W.; Morey, R.A.; Morris, C.P.; Mors, O.; Mortensen, P.B.; Neale, B.M.; Nelson, E.C.; Nordentoft, M.; Norman, S.B.; O'Donnell, M.; Orcutt, H.K.; Panizzon, M.S.; Peters, E.S.; Peterson, A.L.; Peverill, M.; Pietrzak, R.H.; Polusny, M.A.; Rice, J.P.; Ripke, S.; Risbrough, V.B.; Roberts, A.L.; Rothbaum, A.O.; Rothbaum, B.O.; Roy-Byrne, P.; Ruggiero, K.; Rung, A.; Rutten, B.P.F.; Saccone, N.L.; Sanchez, S.E.; Schijven, D.; Seedat, S.; Seligowski, A.V.; Seng, J.S.; Sheerin, C.M.; Silove, D.; Smith, A.K.; Smoller, J.W.; Sponheim, S.R.; Stein, D.J.; Stevens, J.S.; Sumner, J.A.; Teicher, M.H.; Thompson, W.K.; Trapido, E.; Uddin, M.; Ursano, R.J.; Heuvel, L.L. van den; Hooff, M. van; Vermetten, E.; Vinkers, C.H.; Voisey, J.; Wang, Y.P.; Wang, Z.W.; Werge, T.; Williams, M.A.; Williamson, D.E.; Winternitz, S.; Wolf, C.; Wolf, E.J.; Wolff, J.D.; Yehuda, R.; Young, R.M.; Young, K.A.; Zhao, H.; Zoellner, L.A.; Liberzon, I.; Ressler, K.J.; Haas, M.; Koenen, K.C.
• Date: 2019-10-08
• Journal: Nature Communications
• Volume: 10
• DOI: doi:10.1038/s41467-019-12576-w