e-Article
Trauma and posttraumatic stress disorder modulate polygenic predictors of hippocampal and amygdala volume
Document Type
article
Author
Zheng, Yuanchao; Garrett, Melanie E; Sun, Delin; Clarke-Rubright, Emily K; Haswell, Courtney C; Maihofer, Adam X; Elman, Jeremy A; Franz, Carol E; Lyons, Michael J; Kremen, William S; Peverill, Matthew; Sambrook, Kelly; McLaughlin, Katie A; Davenport, Nicholas D; Disner, Seth; Sponheim, Scott R; Andrew, Elpiniki; Korgaonkar, Mayuresh; Bryant, Richard; Varkevisser, Tim; Geuze, Elbert; Coleman, Jonathan; Beckham, Jean C; Kimbrel, Nathan A; Sullivan, Danielle; Miller, Mark; Hayes, Jasmeet; Verfaellie, Mieke; Wolf, Erika; Salat, David; Spielberg, Jeffrey M; Milberg, William; McGlinchey, Regina; Dennis, Emily L; Thompson, Paul M; Medland, Sarah; Jahanshad, Neda; Nievergelt, Caroline M; Ashley-Koch, Allison E; Logue, Mark W; Morey, Rajendra A
Source
Translational Psychiatry. 11(1)
Subject
Language
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