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

Renato Polimanti; Ananda B Amstadter; Murray B Stein; Lynn M Almli; Dewleen G Baker; Laura J Bierut; Bekh Bradley; Lindsay A Farrer; Eric O Johnson; Anthony King; Henry R Kranzler; Adam X Maihofer; John P Rice; Andrea L Roberts; Nancy L Saccone; Hongyu Zhao; Israel Liberzon; Kerry J Ressler; Caroline M Nievergelt; Karestan C Koenen; Joel Gelernter; Psychiatric Genomics Consortium Posttraumatic Stress Disorder Workgroup

doi:10.1186/s13073-017-0491-4

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

Genome Med. 2017 Nov 27;9(1):99. doi: 10.1186/s13073-017-0491-4.

Authors

Renato Polimanti¹, Ananda B Amstadter², Murray B Stein^{3

4

5}, Lynn M Almli⁶, Dewleen G Baker^{3

5}, Laura J Bierut⁷, Bekh Bradley^{6

8}, Lindsay A Farrer⁹, Eric O Johnson¹⁰, Anthony King¹¹, Henry R Kranzler¹², Adam X Maihofer³, John P Rice⁷, Andrea L Roberts¹³, Nancy L Saccone¹⁴, Hongyu Zhao¹⁵, Israel Liberzon^{11

16}, Kerry J Ressler^{17

18}, Caroline M Nievergelt^{3

5}, Karestan C Koenen^{19

20

21}, Joel Gelernter^{22

23}; Psychiatric Genomics Consortium Posttraumatic Stress Disorder Workgroup

Affiliations

¹ Department of Psychiatry, Yale University School of Medicine and VA CT Healthcare Center, 116A2, 950 Campbell Avenue, West Haven, CT, 06516, USA. renato.polimanti@yale.edu.
² Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA.
³ Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
⁴ Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA, USA.
⁵ Veterans Affairs San Diego Healthcare System and Veterans Affairs Center of Excellence for Stress and Mental Health, La Jolla, CA, USA.
⁶ Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, USA.
⁷ Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
⁸ Atlanta VA Medical Center, Atlanta, GA, USA.
⁹ Department of Medicine, Biomedical Genetics Division, Boston University School of Medicine, Boston, MA, USA.
¹⁰ Fellow Program and Behavioral Health and Criminal Justice Division RTI International, Research Triangle Park, NC, USA.
¹¹ Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA.
¹² Department of Psychiatry, University of Pennsylvania Perelman School of Medicine and VISN 4 MIRECC, Crescenz VAMC, Philadelphia, PA, USA.
¹³ Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
¹⁴ Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA.
¹⁵ Department of Biostatistics, Yale University, New Haven, CT, USA.
¹⁶ VA Ann Arbor Health System, Ann Arbor, MI, USA.
¹⁷ Department of Psychiatry, Harvard University, Cambridge, MA, USA.
¹⁸ Department of Psychiatry, McLean Hospital, Belmont, MA, USA.
¹⁹ Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, MA, USA.
²⁰ Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, and Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
²¹ Broad Institute of MIT and Harvard, Stanley Center for Psychiatric Research, Boston, MA, USA.
²² Department of Psychiatry, Yale University School of Medicine and VA CT Healthcare Center, 116A2, 950 Campbell Avenue, West Haven, CT, 06516, USA.
²³ Departments of Neuroscience and of Genetics, Yale University School of Medicine, New Haven, CT, USA.

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.

Keywords: Anthropometric traits; Genetics; Trauma; Women.

MeSH terms

Body Weights and Measures*
Female
Genetic Predisposition to Disease
Humans
Male
Middle Aged
Polymorphism, Single Nucleotide
Reproduction
Risk
Sexual Behavior
Stress Disorders, Post-Traumatic / genetics*

Abstract

MeSH terms

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