Shared genetic architecture of posttraumatic stress disorder with cardiovascular imaging, risk, and diagnoses

Shen J.; Valentim W.; Friligkou E.; Overstreet C.; Choi K.W.; Koller D.; O’Donnell C.J.; Stein M.B.; Gelernter J.; Koenen K.C.; Ressler K.J.; Zwart J.-A.; Zoellner L.A.; Zhao H.; Zervas M.; Zai G.C.; Zai C.C.; Young K.A.; Young R.M.; Yehuda R.; Xiong Y.; Xia Y.; Wolf C.; Wolf E.J.; Winternitz S.; Winsvold B.S.; Williamson D.E.; Williams M.A.; Werge T.; Wendt F.R.; Weber H.; Waszczuk M.; Wang Y.; Wang Z.; Voisey J.; Vinkers C.H.; Vermetten E.; van Rooij S.J.H.; Van Hooff M.; van den Heuvel L.L.; Valdimarsdóttir U.; Ursano R.J.; Uddin M.; Trapido E.; Tiwari A.K.; Thompson W.K.; Teicher M.H.; Sumner J.A.; Stevens J.S.; Stensland S.; Stein D.J.; Sponheim S.R.; Smoller J.W.; Smith A.K.; Silove D.; Sheerin C.M.; Shabalin A.; Seng J.S.; Seedat S.; Seah C.; Santoro M.; Sanchez S.E.; Sampson L.; Salum G.A.; de Viteri S.S.; Rutten B.P.F.; Runz H.; Rung A.; Ruggiero K.J.; Roy-Byrne P.; Rothbaum A.O.; Rothbaum B.O.; Roberts A.L.; Risbrough V.B.; Ratanatharathorn A.; Qin X.-J.; Powers A.; Porjesz B.; Polusny M.A.; Pietrzak R.H.; Peverill M.; Peterson A.L.; Peters E.S.; Panizzon M.S.; Pan P.M.; Orcutt H.K.; O’Donnell M.; Nugent N.R.; Norman S.B.; Nordentoft M.; Nelson E.C.; Mufford M.S.; Mortensen P.B.; Mors O.; Morris C.P.; Morey R.A.; Miller M.W.; Milberg W.; Milani L.; Mikita E.A.; Michopoulos V.; Meyers J.; Mehta D.; Medland S.E.; McLean S.A.; McLaughlin K.A.; McFarlane A.; McAloney K.; Martínez-Levy G.A.; Martin N.G.; Marmar C.; Marchese S.; Maples-Keller J.L.; Makotkine I.; Luykx J.J.; Lupton M.K.; Luft B.J.; Lu Y.; Lori A.; Logue M.W.; Linnstaedt S.D.; Liberzon I.; Lewis C.; Levey D.F.; Lehto K.; Lebois L.A.M.; Lawford B.R.; Kuan P.-F.; Kremen W.S.; Krebs K.; Kranzler H.R.; Kotov R.; Koen N.; King A.P.; Kimbrel N.A.; Khan A.; Kessler R.C.; Kennedy J.L.; Kaufman M.L.; Karstoft K.-I.; Jovanovic T.; Jones I.; Johnson J.; Jenkins G.D.; Javanbakht A.; Jakovljevic M.; Hveem K.; Huckins L.M.; Huang H.; Hougaard D.M.; Hogan K.; Hickie I.B.; Hesselbrock V.; Hemmings S.M.J.; Heath A.C.; Hauser M.A.; Hagenaars S.; Haas M.; Guindalini C.; Grasser L.R.; Gordon S.D.; Goleva S.B.; Goci A.; Gillespie C.F.; Geuze E.; Gelaye B.; Garrett M.E.; Galea S.; Franz C.E.; Forbes D.; Flory J.D.; Feeny N.C.; Feder A.; Farrer L.A.; Fani N.; Fabbri C.; Evans A.; Edenberg H.J.; Kulenovic A.D.; Dyb G.; Domschke K.; Docherty A.R.; Disner S.G.; DiPietro C.P.; Desarnaud F.; deRoon-Cassini T.; Dennis M.F.; Delahanty D.L.; Deckert J.; Davis L.K.; Dalvie S.; Dale A.M.; Cruz-Fuentes C.S.; Coombes B.J.; Colodro-Conde L.; Clouston S.A.P.; Cheema S.; Chatzinakos C.; Caldas-de-Almeida J.M.; Calabrese J.R.; Cahn L.; Børte S.; Børglum A.D.; Bækvad-Hansen M.; Bybjerg-Grauholm J.; Bustamante A.C.; Bryant R.A.; Bressan R.A.; Breen G.; Brandolino A.; Bolger E.A.; Boks M.P.; Bisson J.I.; Bierut L.J.; Biernacka J.M.; Bierer L.M.; Bergner C.; Benjet C.; Belangero S.; Beckham J.C.; Batzler A.; Baker D.G.; Bacanu S.-A.; Babic D.; Avdibegoviç E.; Austin S.B.; Ashley-Koch A.E.; Arbisi P.A.; Andreassen O.A.; Andersen S.B.; Amstadter A.B.; Aaronson C.; Duncan L.E.; Daskalakis N.P.; Coleman J.R.I.; Chen C.-Y.; Atkinson E.G.; Maihofer A.X.; Nievergelt C.M.; Lv H.; Sun L.; Falcone G.J.; Polimanti R.; Pathak G.A. · Nature Communications (2025) · DOI: 10.1038/s41467-025-60487-w

Resumen

Patients with post-traumatic stress disorder face increased cardiovascular risk. This study examines shared genetic regions between post-traumatic stress disorder and 246 cardiovascular conditions across electronic health records, 82 cardiac imaging, and health behaviors defined by Life’s Essential 8. Post-traumatic stress disorder is genetically correlated with cardiovascular diagnoses in 33 regions, imaging traits in 4 regions, and health behaviors in 44 regions. Potentially shared causal variants between post-traumatic stress disorder and 17 cardiovascular conditions were observed in 11 regions. Subsequent observational analysis in AllofUS cohort showed post-traumatic stress disorder is associated with 13 diagnoses even after accounting for socioeconomic factors and depression. Genetically regulated proteome expression in brain and blood tissues identified 33 blood and 122 brain genes shared between the two conditions, revealing neuronal, immune, metabolic, and calcium-related mechanisms, with several genes as targets for existing drugs. These findings exhibit shared risk loci and genes are involved in tissue-specific mechanisms. © The Author(s) 2025.

Instituciones: Universidad Peruana de Ciencias Aplicadas