Zheng, Y., Garrett, M. E., Sun, D., Clarke-Rubright, E. K., Haswell, C. C., Maihofer, A. X., Elman, J. A., Franz, C. E., Lyons, M. J., Kremen, W. S., Peverill, M., Sambrook, K., McLaughlin, K. A., Davenport, N. D., Disner, S., Sponheim, S. R., Andrew, E., Korgaonkar, M., Bryant, R., … Morey, R. A. (2021). Trauma and posttraumatic stress disorder modulate polygenic predictors of hippocampal and amygdala volume. Transl Psychiatry, 11, 637.
NOTES
2158-3188Zheng, YuanchaoOrcid: 0000-0001-7571-3054Garrett, Melanie ESun, DelinOrcid: 0000-0003-3283-423xClarke-Rubright, Emily KHaswell, Courtney CMaihofer, Adam XElman, Jeremy AOrcid: 0000-0002-5840-1769Franz, Carol ELyons, Michael JKremen, William SPeverill, MatthewOrcid: 0000-0002-8257-1004Sambrook, KellyMcLaughlin, Katie ADavenport, Nicholas DDisner, SethOrcid: 0000-0003-3635-9421Sponheim, Scott RAndrew, ElpinikiKorgaonkar, MayureshOrcid: 0000-0002-1339-2221Bryant, RichardOrcid: 0000-0002-9607-819xVarkevisser, TimGeuze, ElbertOrcid: 0000-0003-3479-2379Coleman, JonathanOrcid: 0000-0002-6759-0944Beckham, Jean COrcid: 0000-0001-8746-8949Kimbrel, Nathan ASullivan, DanielleOrcid: 0000-0002-0141-5887Miller, MarkOrcid: 0000-0001-6393-8563Hayes, JasmeetOrcid: 0000-0002-5157-0666Verfaellie, MiekeWolf, ErikaOrcid: 0000-0003-2666-2435Salat, DavidSpielberg, Jeffrey MMilberg, WilliamMcGlinchey, ReginaDennis, Emily LThompson, Paul MMedland, SarahOrcid: 0000-0003-1382-380xJahanshad, NedaNievergelt, Caroline MAshley-Koch, Allison EOrcid: 0000-0001-5409-9155Logue, Mark WMorey, Rajendra AOrcid: 0000-0002-6517-6969R01 AG064955/AG/NIA NIH HHS/United StatesK23 MH073091/MH/NIMH NIH HHS/United StatesR01 MH111671/MH/NIMH NIH HHS/United StatesR01 MH116147/MH/NIMH NIH HHS/United StatesR56 AG058854/AG/NIA NIH HHS/United StatesR01 MH106595/MH/NIMH NIH HHS/United StatesP41 EB015922/EB/NIBIB NIH HHS/United StatesI01 RX000389/RX/RRD VA/United StatesIK2 RX002922/RX/RRD VA/United StatesR01 MH103291/MH/NIMH NIH HHS/United StatesR01 NS086885/NS/NINDS NIH HHS/United StatesI01 CX000748/CX/CSRD VA/United StatesK99 NS096116/NS/NINDS NIH HHS/United StatesIK1 RX002325/RX/RRD VA/United StatesI01 RX000622/RX/RRD VA/United StatesU54 EB020403/EB/NIBIB NIH HHS/United StatesR01 MH117601/MH/NIMH NIH HHS/United StatesR01 AG050595/AG/NIA NIH HHS/United StatesR01 AG059874/AG/NIA NIH HHS/United StatesJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, Non-P.H.S.Transl Psychiatry. 2021 Dec 16;11(1):637. doi: 10.1038/s41398-021-01707-x.
Abstract
The volume of subcortical structures represents a reliable, quantitative, and objective phenotype that captures genetic effects, environmental effects such as trauma, and disease effects such as posttraumatic stress disorder (PTSD). Trauma and PTSD represent potent exposures that may interact with genetic markers to influence brain structure and function. Genetic variants, associated with subcortical volumes in two large normative discovery samples, were used to compute polygenic scores (PGS) for the volume of seven subcortical structures. These were applied to a target sample enriched for childhood trauma and PTSD. Subcortical volume PGS from the discovery sample were strongly associated in our trauma/PTSD enriched sample (n = 7580) with respective subcortical volumes of the hippocampus (p = 1.10 × 10(-20)), thalamus (p = 7.46 × 10(-10)), caudate (p = 1.97 × 10(-18)), putamen (p = 1.7 × 10(-12)), and nucleus accumbens (p = 1.99 × 10(-7)). We found a significant association between the hippocampal volume PGS and hippocampal volume in control subjects from our sample, but was absent in individuals with PTSD (GxE; (beta = -0.10, p = 0.027)). This significant GxE (PGS × PTSD) relationship persisted (p 1 × 10(-19)) in four out of five threshold peaks (0.024, 0.133, 0.487, 0.730, and 0.889) used to calculate hippocampal volume PGSs. We detected similar GxE (G × ChildTrauma) relationships in the amygdala for exposure to childhood trauma (rs4702973; p = 2.16 × 10(-7)) or PTSD (rs10861272; p = 1.78 × 10(-6)) in the CHST11 gene. The hippocampus and amygdala are pivotal brain structures in mediating PTSD symptomatology. Trauma exposure and PTSD modulate the effect of polygenic markers on hippocampal volume (GxE) and the amygdala volume PGS is associated with PTSD risk, which supports the role of amygdala volume as a risk factor for PTSD.
Last updated on 03/06/2023