A putative causal relationship between genetically determined female body shape and posttraumatic stress disorder

• Type of Material: Article
• Authors: Renato Polimanti, Yale University; Anada B. Amstadter, Virginia Commonwealth University; Murray B. Stein, University of California San Diego; Lynn M. Almli, Emory University; Dewleen G. Baker, University of California San Diego; Laura J. Bierut, Washington University; Bekh Bradley-Davino, Emory University; Lindsay A. Farrer, Boston University; Eric O. Johnson, RTI International; Anthony King, University of Michigan; Henry R. Kranzler, University of Pennsylvania; Adam X. Maihofer, University of California San Diego; John P. Rice, Washington Univ; Andrea L. Roberts, Harvard TH Chan Sch Publ Hlth; Nancy L. Saccone, Washington University; Hongyu Zhao, Yale University; Israel Liberzon, University of Michigan; Kerry Ressler, Emory University; Caroline M. Nievergelt, University of California San Diego; Karestan C. Koenen, Harvard TH Chan School of Public Health; Joel Gelernter, Yale University
• Language: English
• Date: 2017-11-27
• Publisher: BioMed Central
• Publication Version: Final Published Version
• Copyright Statement: © 2017 The Author(s).
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s13073-017-0491-4
• Title of Journal or Parent Work: Genome Medicine
• ISSN: 1756-994X
• Volume: 9
• Issue: 1
• Start Page: 99
• End Page: 99
• Grant/Funding Information: This study was supported by National Institutes of Health grants R01 MH106595 and U01 MH109532, and the VA National Center for PTSD Research.
• Keywords: Trauma; Anthropometric traits; MENDELIAN RANDOMIZATION; RISK; GENOME-WIDE ASSOCIATION; Life Sciences & Biomedicine; ADOLESCENT PREGNANCY; Women; LOCI; Genetics & Heredity; TRAITS; SEX-DIFFERENCES; PTSD; Genetics; Science & Technology; WOMEN; SYMPTOMS
• Research Categories: Health Sciences, General; Psychology, General

Abstract

Background: The nature and underlying mechanisms of the observed increased vulnerability to posttraumatic stress disorder (PTSD) in women are unclear. Methods: We 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. Results: We 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 (WC adj ; 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 WC adj . MR-Egger regression intercept analysis showed no evidence of pleiotropic effects in this association (P pleiotropy = 0.979). We also observed associations of genetically determined WC adj with age at first sexual intercourse and number of sexual partners (P = 0.013 and P < 0.001, respectively). Conclusions: There 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.