Abstract
BackgroundThe nature and underlying mechanisms of the observed increased vulnerability to posttraumatic stress disorder (PTSD) in women are unclear.MethodsWe investigated the genetic overlap of PTSD with anthropometric traits and reproductive behaviors and functions in women. The analysis was conducted using female-specific summary statistics from large genome-wide association studies (GWAS) and a cohort of 3577 European American women (966 PTSD cases and 2611 trauma-exposed controls). We applied a high-resolution polygenic score approach and Mendelian randomization analysis to investigate genetic correlations and causal relationships.ResultsWe observed an inverse association of PTSD with genetically determined anthropometric traits related to body shape, independent of body mass index (BMI). The top association was related to BMI-adjusted waist circumference (WCadj; R = -0.079, P < 0.001, Q = 0.011). We estimated a relative decrease of 64.6% (95% confidence interval = 27.5-82.7) in the risk of PTSD per 1-SD increase in WCadj. MR-Egger regression intercept analysis showed no evidence of pleiotropic effects in this association (Ppleiotropy = 0.979). We also observed associations of genetically determined WCadj with age at first sexual intercourse and number of sexual partners (P = 0.013 and P < 0.001, respectively).ConclusionsThere is a putative causal relationship between genetically determined female body shape and PTSD, which could be mediated by evolutionary mechanisms involved in human sexual behaviors.