Skip to main content

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

Publication ,  Journal Article
Nievergelt, CM; Maihofer, AX; Klengel, T; Atkinson, EG; Chen, C-Y; Choi, KW; Coleman, JRI; Dalvie, S; Duncan, LE; Gelernter, J; Levey, DF ...
Published in: Nat Commun
October 8, 2019

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.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

October 8, 2019

Volume

10

Issue

1

Start / End Page

4558

Location

England

Related Subject Headings

  • White People
  • Veterans
  • Ubiquitin-Protein Ligases
  • Stress Disorders, Post-Traumatic
  • Sex Factors
  • Male
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Genetic Loci
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Nievergelt, C. M., Maihofer, A. X., Klengel, T., Atkinson, E. G., Chen, C.-Y., Choi, K. W., … Koenen, K. C. (2019). International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci. Nat Commun, 10(1), 4558. https://doi.org/10.1038/s41467-019-12576-w
Nievergelt, Caroline M., Adam X. Maihofer, Torsten Klengel, Elizabeth G. Atkinson, Chia-Yen Chen, Karmel W. Choi, Jonathan R. I. Coleman, et al. “International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci.Nat Commun 10, no. 1 (October 8, 2019): 4558. https://doi.org/10.1038/s41467-019-12576-w.
Nievergelt CM, Maihofer AX, Klengel T, Atkinson EG, Chen C-Y, Choi KW, et al. International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci. Nat Commun. 2019 Oct 8;10(1):4558.
Nievergelt, Caroline M., et al. “International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci.Nat Commun, vol. 10, no. 1, Oct. 2019, p. 4558. Pubmed, doi:10.1038/s41467-019-12576-w.
Nievergelt CM, Maihofer AX, Klengel T, Atkinson EG, Chen C-Y, Choi KW, Coleman JRI, Dalvie S, Duncan LE, Gelernter J, Levey DF, Logue MW, Polimanti R, Provost AC, Ratanatharathorn A, Stein MB, Torres K, Aiello AE, Almli LM, Amstadter AB, Andersen SB, Andreassen OA, Arbisi PA, Ashley-Koch AE, Austin SB, Avdibegovic E, Babić D, Bækvad-Hansen M, Baker DG, Beckham JC, Bierut LJ, Bisson JI, Boks MP, Bolger EA, Børglum AD, Bradley B, Brashear M, Breen G, Bryant RA, Bustamante AC, Bybjerg-Grauholm J, Calabrese JR, Caldas-de-Almeida JM, Dale AM, Daly MJ, Daskalakis NP, Deckert J, Delahanty DL, Dennis MF, Disner SG, Domschke K, Dzubur-Kulenovic A, Erbes CR, Evans A, Farrer LA, Feeny NC, Flory JD, Forbes D, Franz CE, Galea S, Garrett ME, Gelaye B, Geuze E, Gillespie C, Uka AG, Gordon SD, Guffanti G, Hammamieh R, Harnal S, Hauser MA, Heath AC, Hemmings SMJ, Hougaard DM, Jakovljevic M, Jett M, Johnson EO, Jones I, Jovanovic T, Qin X-J, Junglen AG, Karstoft K-I, Kaufman ML, Kessler RC, Khan A, Kimbrel NA, King AP, Koen N, Kranzler HR, Kremen WS, Lawford BR, Lebois LAM, Lewis CE, Linnstaedt SD, Lori A, Lugonja B, Luykx JJ, Lyons MJ, Maples-Keller J, Marmar C, Martin AR, Martin NG, Maurer D, Mavissakalian MR, McFarlane A, McGlinchey RE, McLaughlin KA, McLean SA, McLeay S, Mehta D, Milberg WP, Miller MW, Morey RA, Morris CP, Mors O, Mortensen PB, Neale BM, Nelson EC, Nordentoft M, Norman SB, O’Donnell M, Orcutt HK, Panizzon MS, Peters ES, Peterson AL, Peverill M, Pietrzak RH, Polusny MA, Rice JP, Ripke S, Risbrough VB, Roberts AL, Rothbaum AO, Rothbaum BO, Roy-Byrne P, Ruggiero K, Rung A, Rutten BPF, Saccone NL, Sanchez SE, Schijven D, Seedat S, Seligowski AV, Seng JS, Sheerin CM, Silove D, Smith AK, Smoller JW, Sponheim SR, Stein DJ, Stevens JS, Sumner JA, Teicher MH, Thompson WK, Trapido E, Uddin M, Ursano RJ, van den Heuvel LL, Van Hooff M, Vermetten E, Vinkers CH, Voisey J, Wang Y, Wang Z, Werge T, Williams MA, Williamson DE, Winternitz S, Wolf C, Wolf EJ, Wolff JD, Yehuda R, Young RM, Young KA, Zhao H, Zoellner LA, Liberzon I, Ressler KJ, Haas M, Koenen KC. International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci. Nat Commun. 2019 Oct 8;10(1):4558.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

October 8, 2019

Volume

10

Issue

1

Start / End Page

4558

Location

England

Related Subject Headings

  • White People
  • Veterans
  • Ubiquitin-Protein Ligases
  • Stress Disorders, Post-Traumatic
  • Sex Factors
  • Male
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Genetic Loci