SNP-exposure (WCadj associations) and SNP-outcome (PTSD associations) coefficients used in the MR analysis. The lines (see legend) represents the results observed considering different methods. (DOCX 383 kb

Adam X. Maihofer

Ananda B. Amstadter

Andrea L. Roberts

Anthony King

Bekh Bradley

Caroline M. Nievergelt

Dewleen G. Baker

Eric O. Johnson

for The Psychiatric Genomics Consortium Posttraumatic Stress Disorder Workgroup

Henry R. Kranzler

Hongyu Zhao

Israel Liberzon

Joel Gelernter

John P. Rice

Karestan C. Koenen

Kerry J. Ressler

Laura J. Bierut

Lindsay A. Farrer

Lynn M. Almli

Murray B. Stein

Nancy L. Saccone

Renato Polimanti

Genome Medicine

Correlation between PTSD PRS and WCadj. (DOCX 12 kb

Renato Polimanti (3043917)

Ananda Amstadter (4710636)

Murray Stein (4048837)

Lynn Almli (4710651)

Dewleen Baker (4710648)

Laura Bierut (4710630)

Bekh Bradley (3577412)

Lindsay Farrer (4710624)

Eric Johnson (788765)

Anthony King (2399878)

Henry Kranzler (4710639)

Adam Maihofer (4710645)

John Rice (215425)

Andrea Roberts (4710642)

Nancy Saccone (4710633)

Hongyu Zhao (4728)

Israel Liberzon (635082)

Kerry Ressler (3503072)

Caroline Nievergelt (4710627)

Karestan Koenen (487438)

Joel Gelernter (83619)

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Additional file 12: of A putative causal relationship between genetically determined female body shape and posttraumatic stress disorder

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 &lt; 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 &lt; 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

Polimanti, Renato

Amstadter, Ananda B

Stein, Murray B

Almli, Lynn M

Baker, Dewleen G

Bierut, Laura J

Bradley, Bekh

Farrer, Lindsay A

Johnson, Eric O

King, Anthony

Kranzler, Henry R

Maihofer, Adam X

Rice, John P

Roberts, Andrea L

Saccone, Nancy L

Zhao, Hongyu

Liberzon, Israel

Ressler, Kerry J

Nievergelt, Caroline M

Koenen, Karestan C

Gelernter, Joel

eScholarship - University of California

English

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

Additional file 11: of A putative causal relationship between genetically determined female body shape and posttraumatic stress disorder

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

Amstadter, Ananda B.

Stein, Murray B.

Almli, Lynn M.

Baker, Dewleen G.

Bierut, Laura J.

Farrer, Lindsay A.

Johnson, Eric O.

Kranzler, Henry R.

Maihofer, Adam X.

Rice, John P.

Roberts, Andrea L.

Saccone, Nancy L.

Ressler, Kerry J.

Nievergelt, Caroline M.

Koenen, Karestan C.

Bisson, Jonathan

Online Research @ Cardiff

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

Directory of Open Access Journals

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. Electronic supplementary material The online version of this article (doi:10.1186/s13073-017-0491-4) contains supplementary material, which is available to authorized users

Harvard University - DASH 

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Additional file 11: of A putative causal relationship between genetically determined female body shape and posttraumatic stress disorder

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eScholarship - University of California

FigShare

Online Research @ Cardiff

Directory of Open Access Journals

Harvard University - DASH

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