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

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

22 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 (US)
Article number	99
Journal	Genome Medicine
Volume	9
Issue number	1
DOIs	https://doi.org/10.1186/s13073-017-0491-4
State	Published - Nov 27 2017

Keywords

Anthropometric traits
Genetics
Trauma
Women

ASJC Scopus subject areas

Molecular Medicine
Molecular Biology
Genetics
Genetics(clinical)

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10.1186/s13073-017-0491-4

Cite this

@article{8e60c9d086f64a6d9366f96d3b0b1d15,

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 Gelernter, {Joel E.} 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",

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

year = "2017",

month = nov,

day = "27",

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

language = "English (US)",

volume = "9",

journal = "Genome Medicine",

issn = "1756-994X",

publisher = "BioMed Central",

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 - Gelernter, Joel E.

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

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 - http://www.scopus.com/inward/record.url?scp=85034975726&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85034975726&partnerID=8YFLogxK

U2 - 10.1186/s13073-017-0491-4

DO - 10.1186/s13073-017-0491-4

M3 - 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

Keywords

ASJC Scopus subject areas

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