Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder.
Caroline M NievergeltAdam X MaihoferElizabeth G AtkinsonChia-Yen ChenKarmel W ChoiJonathan R I ColemanNikolaos P DaskalakisLaramie E DuncanRenato PolimantiCindy AaronsonAnanda B AmstadterSoren B AndersenOle Andreas AndreassenPaul A ArbisiAllison Elizabeth Ashley-KochS Bryn AustinEsmina AvdibegoviçDragan BabićSilviu-Alin BacanuDewleen G BakerAnthony BatzlerJean C BeckhamSintia Nogueira BelangeroCorina BenjetCarisa BergnerLinda M BiererJoanna M BiernackaLaura J BierutJonathan I BissonMarco P M BoksElizabeth A BolgerAmber BrandolinoGerome BreenRodrigo Affonseca BressanRichard A BryantAngela C BustamanteJonas Byberg-GrauholmMarie Bækvad-HansenAnders Dupont BørglumSigrid BørteLeah CahnJoseph R CalabreseJosé Miguel Caldas de AlmeidaChris ChatzinakosSheraz CheemaSean A P CloustonLucia Colodro-CondeBrandon J CoombesCarlos S Cruz-FuentesAnders M DaleShareefa DalvieLea K DavisJürgen DeckertDouglas L DelahantyMichelle F DennisFrank DesarnaudChristopher P DiPietroSeth G DisnerAnna R DochertyKatharina DomschkeGrete DybAlma Džubur KulenovićHoward J EdenbergAlexandra EvansChiara FabbriNegar FaniLindsay A FarrerAdriana FederNorah C FeenyJanine D FloryDavid ForbesCarol E FranzSandro GaleaMelanie E GarrettBizu GelayeJoshua C GrayElbert GeuzeCharles F GillespieSlavina B GolevaScott D GordonAferdita GoçiLana Ruvolo GrasserCamila GuindaliniMagali HaasSaskia HagenaarsMichael A HauserAndrew C HeathSian Megan Joanna HemmingsVictor HesselbrockIan B HickieKelleigh HoganDavid Michael HougaardHailiang HuangLaura M HuckinsKristian HveemMiro JakovljevićArash JavanbakhtGregory D JenkinsJessica JohnsonIan R JonesTanja JovanovicKaren-Inge KarstoftMilissa L KaufmanAyeshah G MohiuddinRonald C KesslerAlaptagin KhanNathan A KimbrelAnthony P KingNastassja KoenRoman KotovHenry R KranzlerKristi KrebsWilliam S KremenPei-Fen KuanBruce R LawfordLauren A M LeboisKelli LehtoDaniel F LeveyCatrin LewisIsreal LiberzonSarah D LinnstaedtMark W LogueAdriana LoriYi LuBenjamin J LuftMichelle K LuptonJurjen J LuykxIouri MakotkineJessica L Maples-KellerShelby MarcheseCharles MarmarNicholas G MartinGabriela A Martínez-LevyKerrie McAloneyAlexander McFarlaneKatie A McLaughlinSamuel A McLeanSarah E MedlandDivya MehtaJacquelyn M MeyersVasiliki MichopoulosElizabeth A MikitaLili A MilaniWilliam MilbergMark W MillerRajendra A MoreyCharles Phillip MorrisOle MorsPreben Bo MortensenMary S MuffordElliot C NelsonMerete NordentoftSonya B NormanNicole R NugentMeaghan Louise O'DonnellHolly K OrcuttPedro M PanMatthew S PanizzonGita A PathakEdward S PetersAlan L PetersonMatthew PeverillRobert H PietrzakMelissa A PolusnyBernice PorjeszAbigail PowersXue-Jun QinAndrew D RatanatharathornVictoria B RisbroughAndrea L RobertsAlex O RothbaumBarbara O RothbaumPeter Roy-ByrneKenneth J RuggieroAriane Lisann RungHeiko RunzBart P F RuttenStacey Saenz de ViteriGiovanni Abrahão SalumLaura SampsonSixto E SanchezMarcos Leite SantoroCarina SeahSoraya SeedatJulia S SengAndrey ShabalinChristina M SheerinDerrick SiloveAlicia K SmithJordan W SmollerScott R SponheimDan J SteinSynne StenslandJennifer S StevenJennifer A SumnerMartin Hersch TeicherWesley K ThompsonArun K TiwariEdward TrapidoMonica UddinRobert J UrsanoUnnur Anna ValdimarsdottirMiranda Van HooffEric VermettenChristiaan H VinkersJoanne VoiseyYunpeng WangZhewu WangMonika WaszczukHeike WeberFrank R WendtThomas M WergeMichelle A WilliamsDouglas E WilliamsonBendik Slagsvold WinsvoldSherry WinternitzChristiane WolfErika J WolfYan XiaYing XiongRachel YehudaKeith A YoungRoss McD YoungClement C ZaiGwyneth C ZaiMark ZervasHongyu ZhaoLori A ZoellnerJohn-Anker ZwartTerri deRoon-CassiniSanne J H van RooijLeigh L van den Heuvelnull nullnull nullnull nullnull nullMurray B SteinKerry James ResslerKarestan C KoenenPublished in: Nature genetics (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.