Maihofer, A. X., Choi, K. W., Coleman, J. R. I., Daskalakis, N. P., Denckla, C. A., Ketema, E., Morey, R. A., Polimanti, R., Ratanatharathorn, A., Torres, K., Wingo, A. P., Zai, C. C., Aiello, A. E., Almli, L. M., Amstadter, A. B., Andersen, S. B., Andreassen, O. A., Arbisi, P. A., Ashley-Koch, A. E., … Nievergelt, C. M. (2022). Enhancing Discovery of Genetic Variants for Posttraumatic Stress Disorder Through Integration of Quantitative Phenotypes and Trauma Exposure Information. Biol Psychiatry, 91, 626-636.
NOTES
1873-2402Maihofer, Adam XChoi, Karmel WColeman, Jonathan R IDaskalakis, Nikolaos PDenckla, Christy AKetema, ElizabethMorey, Rajendra APolimanti, RenatoRatanatharathorn, AndrewTorres, KatyWingo, Aliza PZai, Clement CAiello, Allison EAlmli, Lynn MAmstadter, Ananda BAndersen, Soren BAndreassen, Ole AArbisi, Paul AAshley-Koch, Allison EAustin, S BrynAvdibegović, EsminaBorglum, Anders DBabić, DraganBækvad-Hansen, MarieBaker, Dewleen GBeckham, Jean CBierut, Laura JBisson, Jonathan IBoks, Marco PBolger, Elizabeth ABradley, BekhBrashear, MeghanBreen, GeromeBryant, Richard ABustamante, Angela CBybjerg-Grauholm, JonasCalabrese, Joseph RCaldas-de-Almeida, José MChen, Chia-YenDale, Anders MDalvie, ShareefaDeckert, JürgenDelahanty, Douglas LDennis, Michelle FDisner, Seth GDomschke, KatharinaDuncan, Laramie EDžubur Kulenović, AlmaErbes, Christopher REvans, AlexandraFarrer, Lindsay AFeeny, Norah CFlory, Janine DForbes, DavidFranz, Carol EGalea, SandroGarrett, Melanie EGautam, AartiGelaye, BizuGelernter, JoelGeuze, ElbertGillespie, Charles FGoçi, AferditaGordon, Scott DGuffanti, GuiaHammamieh, RashaHauser, Michael AHeath, Andrew CHemmings, Sian M JHougaard, David MichaelJakovljević, MiroJett, MartiJohnson, Eric OttoJones, IanJovanovic, TanjaQin, Xue-JunKarstoft, Karen-IngeKaufman, Milissa LKessler, Ronald CKhan, AlaptaginKimbrel, Nathan AKing, Anthony PKoen, NastassjaKranzler, Henry RKremen, William SLawford, Bruce RLebois, Lauren A MLewis, CatrinLiberzon, IsraelLinnstaedt, Sarah DLogue, Mark WLori, AdrianaLugonja, BožoLuykx, Jurjen JLyons, Michael JMaples-Keller, Jessica LMarmar, CharlesMartin, Nicholas GMaurer, DouglasMavissakalian, Matig RMcFarlane, AlexanderMcGlinchey, Regina EMcLaughlin, Katie AMcLean, Samuel AMehta, DivyaMellor, RebeccaMichopoulos, VasilikiMilberg, WilliamMiller, Mark WMorris, Charles PhillipMors, OleMortensen, Preben BNelson, Elliot CNordentoft, MereteNorman, Sonya BO'Donnell, MeaghanOrcutt, Holly KPanizzon, Matthew SPeters, Edward SPeterson, Alan LPeverill, MatthewPietrzak, Robert HPolusny, Melissa ARice, John PRisbrough, Victoria BRoberts, Andrea LRothbaum, Alex ORothbaum, Barbara ORoy-Byrne, PeterRuggiero, Kenneth JRung, ArianeRutten, Bart P FSaccone, Nancy LSanchez, Sixto ESchijven, DickSeedat, SorayaSeligowski, Antonia VSeng, Julia SSheerin, Christina MSilove, DerrickSmith, Alicia KSmoller, Jordan WSponheim, Scott RStein, Dan JStevens, Jennifer STeicher, Martin HThompson, Wesley KTrapido, EdwardUddin, MonicaUrsano, Robert Jvan den Heuvel, Leigh LuellaVan Hooff, MirandaVermetten, EricVinkers, Christiaan HVoisey, JoanneWang, YunpengWang, ZhewuWerge, ThomasWilliams, Michelle AWilliamson, Douglas EWinternitz, SherryWolf, ChristianeWolf, Erika JYehuda, RachelYoung, Keith AYoung, Ross McDZhao, HongyuZoellner, Lori AHaas, MagaliLasseter, HeatherProvost, Allison CSalem, Rany MSebat, JonathanShaffer, Richard AWu, TianyingRipke, StephanDaly, Mark JRessler, Kerry JKoenen, Karestan CStein, Murray BNievergelt, Caroline MIK2 RX002922/RX/RRD VA/United StatesU01 MH109539/MH/NIMH NIH HHS/United StatesR01 MH106595/MH/NIMH NIH HHS/United StatesK01 MH118467/MH/NIMH NIH HHS/United StatesR01 AG064955/AG/NIA NIH HHS/United StatesK23 MH117278/MH/NIMH NIH HHS/United StatesR01 AG022381/AG/NIA NIH HHS/United StatesR01 AG050595/AG/NIA NIH HHS/United StatesJournal ArticleMeta-AnalysisResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, Non-P.H.S.Biol Psychiatry. 2022 Apr 1;91(7):626-636. doi: 10.1016/j.biopsych.2021.09.020. Epub 2021 Sep 28.
Abstract
BACKGROUND: Posttraumatic stress disorder (PTSD) is heritable and a potential consequence of exposure to traumatic stress. Evidence suggests that a quantitative approach to PTSD phenotype measurement and incorporation of lifetime trauma exposure (LTE) information could enhance the discovery power of PTSD genome-wide association studies (GWASs). METHODS: A GWAS on PTSD symptoms was performed in 51 cohorts followed by a fixed-effects meta-analysis (N = 182,199 European ancestry participants). A GWAS of LTE burden was performed in the UK Biobank cohort (N = 132,988). Genetic correlations were evaluated with linkage disequilibrium score regression. Multivariate analysis was performed using Multi-Trait Analysis of GWAS. Functional mapping and annotation of leading loci was performed with FUMA. Replication was evaluated using the Million Veteran Program GWAS of PTSD total symptoms. RESULTS: GWASs of PTSD symptoms and LTE burden identified 5 and 6 independent genome-wide significant loci, respectively. There was a 72% genetic correlation between PTSD and LTE. PTSD and LTE showed largely similar patterns of genetic correlation with other traits, albeit with some distinctions. Adjusting PTSD for LTE reduced PTSD heritability by 31%. Multivariate analysis of PTSD and LTE increased the effective sample size of the PTSD GWAS by 20% and identified 4 additional loci. Four of these 9 PTSD loci were independently replicated in the Million Veteran Program. CONCLUSIONS: Through using a quantitative trait measure of PTSD, we identified novel risk loci not previously identified using prior case-control analyses. PTSD and LTE have a high genetic overlap that can be leveraged to increase discovery power through multivariate methods.
Last updated on 03/06/2023