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

for The 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

for The Psychiatric Genomics Consortium Posttraumatic Stress Disorder Workgroup

Yale University
Virginia Commonwealth University
Department of Psychiatry
University of California at San Diego
Department of Family Medicine and Public Health
Department of Veterans Affairs
Emory University
Department of Psychiatry
Washington University St. Louis
Biomedical Genetics
Boston University
RTI International
University of Michigan, Ann Arbor
Department of Psychiatry
University of Pennsylvania
Department of Environmental Health
Harvard University
Department of Social and Behavioral Sciences
Department of Genetics
Department of Biostatistics
Department of Epidemiology
Department of Psychiatry
Massachusetts General Hospital
Broad Institute
Departments of Genetics and Neuroscience
Department of Psychiatry
Stanford University
Analytic and Translational Genetics Unit
Department of Epidemiology
Columbia University
Department of Epidemiology
University of North Carolina at Chapel Hill
Division of Infectious Diseases
Duke University
Durham Veterans Affairs Health Care System
Department of Psychiatry and Behavioral Sciences
Division of Psychological Medicine and Clinical Neurosciences
Cardiff University
Division of Human Genetics
University of Cape Town
Department of Psychiatry
McLean Hospital
Department of Health Care Policy
Department of Psychiatry and Mental Health
VA Medical Center
Durham Veterans Affairs Medical Center
Division of Behavioral Genetics
Rhode Island Hospital
Brown University
Department of Psychiatry and Psychotherapy
Charité – Universitätsmedizin Berlin
Center for Cardiovascular Behavioral Health
University of Illinois at Urbana-Champaign
Department of Psychiatry
Uniformed Services University of the Health Sciences
Icahn School of Medicine at Mount Sinai
Department of Neuroscience

Research output: Contribution to journal › Article › peer-review

24 Scopus citations

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.

Original language	English
Article number	99
Journal	Genome Medicine
Volume	9
Issue number	1
DOIs	https://doi.org/10.1186/s13073-017-0491-4
State	Published - 27 Nov 2017
Externally published	Yes

Funding

Funders	Funder number
VA National Center for PTSD Research
National Institutes of Health	U01 MH109532
National Institute of Mental Health	R01MH106595

Keywords

Anthropometric traits
Genetics
Trauma
Women

Access to Document

10.1186/s13073-017-0491-4

Cite this

@article{0206c9bdf494473d84a58052f4756b17,

title = "A putative causal relationship between genetically determined female body shape and posttraumatic stress disorder",

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 (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). 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",

author = "\{for The Psychiatric Genomics Consortium Posttraumatic Stress Disorder Workgroup\} and Renato Polimanti and Amstadter, \{Ananda B.\} and Stein, \{Murray B.\} and Almli, \{Lynn M.\} and Baker, \{Dewleen G.\} and Bierut, \{Laura J.\} and Bekh Bradley and Farrer, \{Lindsay A.\} and Johnson, \{Eric O.\} and Anthony King and Kranzler, \{Henry R.\} and Maihofer, \{Adam X.\} and Rice, \{John P.\} and Roberts, \{Andrea L.\} and Saccone, \{Nancy L.\} and Hongyu Zhao and Israel Liberzon and Nievergelt, \{Caroline M.\} and Koenen, \{Karestan C.\} and Joel Gelernter and Duncan, \{Laramie E.\} and Chen, \{Chia Yen\} and Andrew Ratanatharathorn and Aiello, \{Allison E.\} and Ashley-Koch, \{Allison E.\} and Garrett, \{Melanie E.\} and Hauser, \{Michael A.\} and Beckham, \{Jean C.\} and Kimbrel, \{Nathan A.\} and Jonathan Bisson and Shareefa Dalvie and Sandro Galea and Guia Guffanti and Ressler, \{Kerry J.\} and Kessler, \{Ronald C.\} and Nastassja Koen and Stein, \{Daniel J.\} and Logue, \{Mark W.\} and Miller, \{Mark W.\} and Martin, \{Alicia R.\} and Morey, \{Rajendra A.\} and Nugent, \{Nicole R.\} and Stephan Ripke and Smoller, \{Jordan W.\} and Sumner, \{Jennifer A.\} and Monica Uddin and Ursano, \{Robert J.\} and Wildman, \{Derek E.\} and Rachel Yehuda and Daly, \{Mark J.\}",

note = "Publisher Copyright: {\textcopyright} 2017 The Author(s).",

year = "2017",

month = nov,

day = "27",

doi = "10.1186/s13073-017-0491-4",

language = "אנגלית",

volume = "9",

journal = "Genome Medicine",

issn = "1756-994X",

publisher = "BioMed Central Ltd.",

number = "1",

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TY - JOUR

T1 - A putative causal relationship between genetically determined female body shape and posttraumatic stress disorder

AU - for The Psychiatric Genomics Consortium Posttraumatic Stress Disorder Workgroup

AU - Polimanti, Renato

AU - Amstadter, Ananda B.

AU - Stein, Murray B.

AU - Almli, Lynn M.

AU - Baker, Dewleen G.

AU - Bierut, Laura J.

AU - Bradley, Bekh

AU - Farrer, Lindsay A.

AU - Johnson, Eric O.

AU - King, Anthony

AU - Kranzler, Henry R.

AU - Maihofer, Adam X.

AU - Rice, John P.

AU - Roberts, Andrea L.

AU - Saccone, Nancy L.

AU - Zhao, Hongyu

AU - Liberzon, Israel

AU - Nievergelt, Caroline M.

AU - Koenen, Karestan C.

AU - Gelernter, Joel

AU - Duncan, Laramie E.

AU - Chen, Chia Yen

AU - Ratanatharathorn, Andrew

AU - Aiello, Allison E.

AU - Ashley-Koch, Allison E.

AU - Garrett, Melanie E.

AU - Hauser, Michael A.

AU - Beckham, Jean C.

AU - Kimbrel, Nathan A.

AU - Bisson, Jonathan

AU - Dalvie, Shareefa

AU - Galea, Sandro

AU - Guffanti, Guia

AU - Ressler, Kerry J.

AU - Kessler, Ronald C.

AU - Koen, Nastassja

AU - Stein, Daniel J.

AU - Logue, Mark W.

AU - Miller, Mark W.

AU - Martin, Alicia R.

AU - Morey, Rajendra A.

AU - Nugent, Nicole R.

AU - Ripke, Stephan

AU - Smoller, Jordan W.

AU - Sumner, Jennifer A.

AU - Uddin, Monica

AU - Ursano, Robert J.

AU - Wildman, Derek E.

AU - Yehuda, Rachel

AU - Daly, Mark J.

PY - 2017/11/27

Y1 - 2017/11/27

N2 - 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 (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). 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.

AB - 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 (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). 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.

KW - Anthropometric traits

KW - Genetics

KW - Trauma

KW - Women

UR - https://www.scopus.com/pages/publications/85034975726

U2 - 10.1186/s13073-017-0491-4

DO - 10.1186/s13073-017-0491-4

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 29178946

AN - SCOPUS:85034975726

SN - 1756-994X

VL - 9

JO - Genome Medicine

JF - Genome Medicine

IS - 1

M1 - 99

ER -

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

Abstract

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Keywords

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