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Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder.

Publication ,  Journal Article
Nievergelt, CM; Maihofer, AX; Atkinson, EG; Chen, C-Y; Choi, KW; Coleman, JRI; Daskalakis, NP; Duncan, LE; Polimanti, R; Aaronson, C; Babić, D ...
Published in: Nat Genet
May 2024

Post-traumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 new). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (for example, GRIA1, GRM8 and CACNA1E), developmental, axon guidance and transcription factors (for example, FOXP2, EFNA5 and DCC), synaptic structure and function genes (for example, PCLO, NCAM1 and PDE4B) and endocrine or immune regulators (for example, ESR1, TRAF3 and TANK). Additional top genes influence stress, immune, fear and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation.

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Published In

Nat Genet

DOI

EISSN

1546-1718

Publication Date

May 2024

Volume

56

Issue

5

Start / End Page

792 / 808

Location

United States

Related Subject Headings

  • White People
  • White
  • Stress Disorders, Post-Traumatic
  • Polymorphism, Single Nucleotide
  • Neurobiology
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Genetic Loci
  • Developmental Biology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Nievergelt, C. M., Maihofer, A. X., Atkinson, E. G., Chen, C.-Y., Choi, K. W., Coleman, J. R. I., … Koenen, K. C. (2024). Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder. Nat Genet, 56(5), 792–808. https://doi.org/10.1038/s41588-024-01707-9
Nievergelt, Caroline M., Adam X. Maihofer, Elizabeth G. Atkinson, Chia-Yen Chen, Karmel W. Choi, Jonathan R. I. Coleman, Nikolaos P. Daskalakis, et al. “Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder.Nat Genet 56, no. 5 (May 2024): 792–808. https://doi.org/10.1038/s41588-024-01707-9.
Nievergelt CM, Maihofer AX, Atkinson EG, Chen C-Y, Choi KW, Coleman JRI, et al. Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder. Nat Genet. 2024 May;56(5):792–808.
Nievergelt, Caroline M., et al. “Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder.Nat Genet, vol. 56, no. 5, May 2024, pp. 792–808. Pubmed, doi:10.1038/s41588-024-01707-9.
Nievergelt CM, Maihofer AX, Atkinson EG, Chen C-Y, Choi KW, Coleman JRI, Daskalakis NP, Duncan LE, Polimanti R, Aaronson C, Amstadter AB, Andersen SB, Andreassen OA, Arbisi PA, Ashley-Koch AE, Austin SB, Avdibegoviç E, Babić D, Bacanu S-A, Baker DG, Batzler A, Beckham JC, Belangero S, Benjet C, Bergner C, Bierer LM, Biernacka JM, Bierut LJ, Bisson JI, Boks MP, Bolger EA, Brandolino A, Breen G, Bressan RA, Bryant RA, Bustamante AC, Bybjerg-Grauholm J, Bækvad-Hansen M, Børglum AD, Børte S, Cahn L, Calabrese JR, Caldas-de-Almeida JM, Chatzinakos C, Cheema S, Clouston SAP, Colodro-Conde L, Coombes BJ, Cruz-Fuentes CS, Dale AM, Dalvie S, Davis LK, Deckert J, Delahanty DL, Dennis MF, Desarnaud F, DiPietro CP, Disner SG, Docherty AR, Domschke K, Dyb G, Kulenović AD, Edenberg HJ, Evans A, Fabbri C, Fani N, Farrer LA, Feder A, Feeny NC, Flory JD, Forbes D, Franz CE, Galea S, Garrett ME, Gelaye B, Gelernter J, Geuze E, Gillespie CF, Goleva SB, Gordon SD, Goçi A, Grasser LR, Guindalini C, Haas M, Hagenaars S, Hauser MA, Heath AC, Hemmings SMJ, Hesselbrock V, Hickie IB, Hogan K, Hougaard DM, Huang H, Huckins LM, Hveem K, Jakovljević M, Javanbakht A, Jenkins GD, Johnson J, Jones I, Jovanovic T, Karstoft K-I, Kaufman ML, Kennedy JL, Kessler RC, Khan A, Kimbrel NA, King AP, Koen N, Kotov R, Kranzler HR, Krebs K, Kremen WS, Kuan P-F, Lawford BR, Lebois LAM, Lehto K, Levey DF, Lewis C, Liberzon I, Linnstaedt SD, Logue MW, Lori A, Lu Y, Luft BJ, Lupton MK, Luykx JJ, Makotkine I, Maples-Keller JL, Marchese S, Marmar C, Martin NG, Martínez-Levy GA, McAloney K, McFarlane A, McLaughlin KA, McLean SA, Medland SE, Mehta D, Meyers J, Michopoulos V, Mikita EA, Milani L, Milberg W, Miller MW, Morey RA, Morris CP, Mors O, Mortensen PB, Mufford MS, Nelson EC, Nordentoft M, Norman SB, Nugent NR, O’Donnell M, Orcutt HK, Pan PM, Panizzon MS, Pathak GA, Peters ES, Peterson AL, Peverill M, Pietrzak RH, Polusny MA, Porjesz B, Powers A, Qin X-J, Ratanatharathorn A, Risbrough VB, Roberts AL, Rothbaum AO, Rothbaum BO, Roy-Byrne P, Ruggiero KJ, Rung A, Runz H, Rutten BPF, de Viteri SS, Salum GA, Sampson L, Sanchez SE, Santoro M, Seah C, Seedat S, Seng JS, Shabalin A, Sheerin CM, Silove D, Smith AK, Smoller JW, Sponheim SR, Stein DJ, Stensland S, Stevens JS, Sumner JA, Teicher MH, Thompson WK, Tiwari AK, Trapido E, Uddin M, Ursano RJ, Valdimarsdóttir U, Van Hooff M, Vermetten E, Vinkers CH, Voisey J, Wang Y, Wang Z, Waszczuk M, Weber H, Wendt FR, Werge T, Williams MA, Williamson DE, Winsvold BS, Winternitz S, Wolf C, Wolf EJ, Xia Y, Xiong Y, Yehuda R, Young KA, Young RM, Zai CC, Zai GC, Zervas M, Zhao H, Zoellner LA, Zwart J-A, deRoon-Cassini T, van Rooij SJH, van den Heuvel LL, AURORA Study, Estonian Biobank Research Team, FinnGen Investigators, HUNT All-In Psychiatry, Stein MB, Ressler KJ, Koenen KC. Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder. Nat Genet. 2024 May;56(5):792–808.

Published In

Nat Genet

DOI

EISSN

1546-1718

Publication Date

May 2024

Volume

56

Issue

5

Start / End Page

792 / 808

Location

United States

Related Subject Headings

  • White People
  • White
  • Stress Disorders, Post-Traumatic
  • Polymorphism, Single Nucleotide
  • Neurobiology
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Genetic Loci
  • Developmental Biology