Association of Economic Status and Educational Attainment With Posttraumatic Stress Disorder: A Mendelian Randomization Study

Renato Polimanti; Andrew Ratanatharathorn; Adam X. Maihofer; Karmel W. Choi; Murray B. Stein; Rajendra A. Morey; Mark W. Logue; Caroline M. Nievergelt; Dan J. Stein; Karestan C. Koenen; Joel Gelernter; Caroline M. Nievergelt; Adam X. Maihofer; Torsten Klengel; Elizabeth G. Atkinson; Chia-Yen Chen; Jonathan R. I. Coleman; Shareefa Dalvie; Laramie E. Duncan; Mark W. Logue; Allison C. Provost; Andrew Ratanatharathorn; Murray B. Stein; Katy Torres; Allison E. Aiello; Lynn M. Almli; Ananda B. Amstadter; Soren B. Andersen; Ole A. Andreassen; Paul A. Arbisi; Allison E. Ashley-Koch; S. Bryn Austin; Esmina Avdibegovic; Dragan Babic; Marie Baekvad-Hansen; Dewleen G. Baker; Jean C. Beckham; Laura J. Bierut; Jonathan I. Bisson; Marco P. Boks; Elizabeth A. Bolger; Anders D. Borglum; Bekh Bradley; Megan Brashear; Gerome Breen; Richard A. Bryant; Angela C. Bustamante; Jonas Bybjerg-Grauholm; Joseph R. Calabrese; Bart P. F. Rutten; Schizophrenia Working Group of the Psychiatric Genomics Consortium

doi:10.1001/jamanetworkopen.2019.3447

Association of Economic Status and Educational Attainment With Posttraumatic Stress Disorder: A Mendelian Randomization Study

Renato Polimanti^*, Andrew Ratanatharathorn, Adam X. Maihofer, Karmel W. Choi, Murray B. Stein, Rajendra A. Morey, Mark W. Logue, Caroline M. Nievergelt, Dan J. Stein, Karestan C. Koenen, Joel Gelernter, Caroline M. Nievergelt, Adam X. Maihofer, Torsten Klengel, Elizabeth G. Atkinson, Chia-Yen Chen, Jonathan R. I. Coleman, Shareefa Dalvie, Laramie E. Duncan, Mark W. LogueAllison C. Provost, Andrew Ratanatharathorn, Murray B. Stein, Katy Torres, Allison E. Aiello, Lynn M. Almli, Ananda B. Amstadter, Soren B. Andersen, Ole A. Andreassen, Paul A. Arbisi, Allison E. Ashley-Koch, S. Bryn Austin, Esmina Avdibegovic, Dragan Babic, Marie Baekvad-Hansen, Dewleen G. Baker, Jean C. Beckham, Laura J. Bierut, Jonathan I. Bisson, Marco P. Boks, Elizabeth A. Bolger, Anders D. Borglum, Bekh Bradley, Megan Brashear, Gerome Breen, Richard A. Bryant, Angela C. Bustamante, Jonas Bybjerg-Grauholm, Joseph R. Calabrese, Bart P. F. Rutten, Schizophrenia Working Group of the Psychiatric Genomics Consortium

^*Corresponding author for this work

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

Abstract

IMPORTANCE There is a well-established negative association of educational attainment (EA) and other traits related to cognitive ability with posttraumatic stress disorder (PTSD), but the underlying mechanisms are poorly understood.

OBJECTIVES To investigate the association of PTSD with traits related to EA.

DESIGN, SETTING, AND PARTICIPANTS Genetic correlation, polygenic risk scoring, and mendelian randomization (MR) were conducted including 23 185 individuals with PTSD and 151 309 control participants from the Psychiatric Genomics Consortium for PTSD and up to 1 131 881 individuals assessed for EA and related traits from UK Biobank, 23andMe, and the Social Science Genetic Association Consortium. Data were analyzed from July 3 through November 19, 2018.

MAIN OUTCOMES AND MEASURES Genetic correlation obtained from linkage disequilibrium score regression, phenotypic variance explained by polygenic risk scores, and association estimates from MR.

RESULTS Summary association data from multiple genome-wide association studies were available for a total of 1 180 352 participants (634 391 [53.7%] women). Posttraumatic stress disorder showed negative genetic correlations with EA (r(g) = -0.26; SE = 0.05; P = 4.60 x 10(-8)). Mendelian randomization analysis, conducting considering a random-effects inverse-variance weighted method, indicated that EA has a negative association with PTSD (beta = -0.23; 95% CI, -0.07 to -0.39; P = .004). Investigating potential mediators of the EA-PTSD association, propensity for trauma exposure and risk-taking behaviors were observed as risk factors for PTSD independent of EA (trauma exposure: beta = 0.37; 95% CI, 0.19 to 0.52; P = 2.57 x 10(-5); risk-taking: beta = 0.76; 95% CI, 0.38 to 1.13; P = 1.13 x 10(-4)), while income may mediate the association of EA with PSTD (MR income: beta = -0.18; 95% CI, -0.29 to -0.07; P =.001; MR EA: beta = -0.23; 95% CI, -0.39 to -0.07; P =.004; multivariable MR income: beta = -0.32; 95% CI, -0.57 to 0.07; P = .02; multivariable MR EA: beta = -0.04; 95% CI, -0.29 to 0.21; SE, 0.13; P = .79).

CONCLUSIONS AND RELEVANCE Large-scale genomic data sets add further evidence to the negative association of EA with PTSD, also supporting the role of economic status as a mediator in the association observed.

Original language	English
Article number	193447
Pages (from-to)	1-17
Number of pages	17
Journal	Jama network open
Volume	2
Issue number	5
DOIs	https://doi.org/10.1001/jamanetworkopen.2019.3447
Publication status	Published - May 2019

Keywords

COGNITIVE-ABILITY
GENETIC-VARIANTS
RNA-SEQ
RISK
SCHIZOPHRENIA
TRAJECTORIES
DIVERSITY
PTSD

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Polimanti, R., Ratanatharathorn, A., Maihofer, A. X., Choi, K. W., Stein, M. B., Morey, R. A., Logue, M. W., Nievergelt, C. M., Stein, D. J., Koenen, K. C., Gelernter, J., Nievergelt, C. M., Maihofer, A. X., Klengel, T., Atkinson, E. G., Chen, C.-Y., Coleman, J. R. I., Dalvie, S., Duncan, L. E., ... Schizophrenia Working Group of the Psychiatric Genomics Consortium (2019). Association of Economic Status and Educational Attainment With Posttraumatic Stress Disorder: A Mendelian Randomization Study. Jama network open, 2(5), 1-17. Article 193447. https://doi.org/10.1001/jamanetworkopen.2019.3447

@article{9b872a4a48bd4aa88ed1b6942ca9ea1c,

title = "Association of Economic Status and Educational Attainment With Posttraumatic Stress Disorder: A Mendelian Randomization Study",

abstract = "IMPORTANCE There is a well-established negative association of educational attainment (EA) and other traits related to cognitive ability with posttraumatic stress disorder (PTSD), but the underlying mechanisms are poorly understood.OBJECTIVES To investigate the association of PTSD with traits related to EA.DESIGN, SETTING, AND PARTICIPANTS Genetic correlation, polygenic risk scoring, and mendelian randomization (MR) were conducted including 23 185 individuals with PTSD and 151 309 control participants from the Psychiatric Genomics Consortium for PTSD and up to 1 131 881 individuals assessed for EA and related traits from UK Biobank, 23andMe, and the Social Science Genetic Association Consortium. Data were analyzed from July 3 through November 19, 2018.MAIN OUTCOMES AND MEASURES Genetic correlation obtained from linkage disequilibrium score regression, phenotypic variance explained by polygenic risk scores, and association estimates from MR.RESULTS Summary association data from multiple genome-wide association studies were available for a total of 1 180 352 participants (634 391 [53.7%] women). Posttraumatic stress disorder showed negative genetic correlations with EA (r(g) = -0.26; SE = 0.05; P = 4.60 x 10(-8)). Mendelian randomization analysis, conducting considering a random-effects inverse-variance weighted method, indicated that EA has a negative association with PTSD (beta = -0.23; 95% CI, -0.07 to -0.39; P = .004). Investigating potential mediators of the EA-PTSD association, propensity for trauma exposure and risk-taking behaviors were observed as risk factors for PTSD independent of EA (trauma exposure: beta = 0.37; 95% CI, 0.19 to 0.52; P = 2.57 x 10(-5); risk-taking: beta = 0.76; 95% CI, 0.38 to 1.13; P = 1.13 x 10(-4)), while income may mediate the association of EA with PSTD (MR income: beta = -0.18; 95% CI, -0.29 to -0.07; P =.001; MR EA: beta = -0.23; 95% CI, -0.39 to -0.07; P =.004; multivariable MR income: beta = -0.32; 95% CI, -0.57 to 0.07; P = .02; multivariable MR EA: beta = -0.04; 95% CI, -0.29 to 0.21; SE, 0.13; P = .79).CONCLUSIONS AND RELEVANCE Large-scale genomic data sets add further evidence to the negative association of EA with PTSD, also supporting the role of economic status as a mediator in the association observed.",

keywords = "COGNITIVE-ABILITY, GENETIC-VARIANTS, RNA-SEQ, RISK, SCHIZOPHRENIA, TRAJECTORIES, DIVERSITY, PTSD",

author = "Renato Polimanti and Andrew Ratanatharathorn and Maihofer, {Adam X.} and Choi, {Karmel W.} and Stein, {Murray B.} and Morey, {Rajendra A.} and Logue, {Mark W.} and Nievergelt, {Caroline M.} and Stein, {Dan J.} and Koenen, {Karestan C.} and Joel Gelernter and Nievergelt, {Caroline M.} and Maihofer, {Adam X.} and Torsten Klengel and Atkinson, {Elizabeth G.} and Chia-Yen Chen and Coleman, {Jonathan R. I.} and Shareefa Dalvie and Duncan, {Laramie E.} and Logue, {Mark W.} and Provost, {Allison C.} and Andrew Ratanatharathorn and Stein, {Murray B.} and Katy Torres and Aiello, {Allison E.} and Almli, {Lynn M.} and Amstadter, {Ananda B.} and Andersen, {Soren B.} and Andreassen, {Ole A.} and Arbisi, {Paul A.} and Ashley-Koch, {Allison E.} and Austin, {S. Bryn} and Esmina Avdibegovic and Dragan Babic and Marie Baekvad-Hansen and Baker, {Dewleen G.} and Beckham, {Jean C.} and Bierut, {Laura J.} and Bisson, {Jonathan I.} and Boks, {Marco P.} and Bolger, {Elizabeth A.} and Borglum, {Anders D.} and Bekh Bradley and Megan Brashear and Gerome Breen and Bryant, {Richard A.} and Bustamante, {Angela C.} and Jonas Bybjerg-Grauholm and Calabrese, {Joseph R.} and Rutten, {Bart P. F.} and {Schizophrenia Working Group of the Psychiatric Genomics Consortium}",

year = "2019",

month = may,

doi = "10.1001/jamanetworkopen.2019.3447",

language = "English",

volume = "2",

pages = "1--17",

journal = "Jama network open",

issn = "2574-3805",

publisher = "American Medical Association",

number = "5",

}

Polimanti, R, Ratanatharathorn, A, Maihofer, AX, Choi, KW, Stein, MB, Morey, RA, Logue, MW, Nievergelt, CM, Stein, DJ, Koenen, KC, Gelernter, J, Nievergelt, CM, Maihofer, AX, Klengel, T, Atkinson, EG, Chen, C-Y, Coleman, JRI, Dalvie, S, Duncan, LE, Logue, MW, Provost, AC, Ratanatharathorn, A, Stein, MB, Torres, K, Aiello, AE, Almli, LM, Amstadter, AB, Andersen, SB, Andreassen, OA, Arbisi, PA, Ashley-Koch, AE, Austin, SB, Avdibegovic, E, Babic, D, Baekvad-Hansen, M, Baker, DG, Beckham, JC, Bierut, LJ, Bisson, JI, Boks, MP, Bolger, EA, Borglum, AD, Bradley, B, Brashear, M, Breen, G, Bryant, RA, Bustamante, AC, Bybjerg-Grauholm, J, Calabrese, JR, Rutten, BPF & Schizophrenia Working Group of the Psychiatric Genomics Consortium 2019, 'Association of Economic Status and Educational Attainment With Posttraumatic Stress Disorder: A Mendelian Randomization Study', Jama network open, vol. 2, no. 5, 193447, pp. 1-17. https://doi.org/10.1001/jamanetworkopen.2019.3447

TY - JOUR

T1 - Association of Economic Status and Educational Attainment With Posttraumatic Stress Disorder

T2 - A Mendelian Randomization Study

AU - Polimanti, Renato

AU - Ratanatharathorn, Andrew

AU - Maihofer, Adam X.

AU - Choi, Karmel W.

AU - Stein, Murray B.

AU - Morey, Rajendra A.

AU - Logue, Mark W.

AU - Nievergelt, Caroline M.

AU - Stein, Dan J.

AU - Koenen, Karestan C.

AU - Gelernter, Joel

AU - Nievergelt, Caroline M.

AU - Maihofer, Adam X.

AU - Klengel, Torsten

AU - Atkinson, Elizabeth G.

AU - Chen, Chia-Yen

AU - Coleman, Jonathan R. I.

AU - Dalvie, Shareefa

AU - Duncan, Laramie E.

AU - Logue, Mark W.

AU - Provost, Allison C.

AU - Ratanatharathorn, Andrew

AU - Stein, Murray B.

AU - Torres, Katy

AU - Aiello, Allison E.

AU - Almli, Lynn M.

AU - Amstadter, Ananda B.

AU - Andersen, Soren B.

AU - Andreassen, Ole A.

AU - Arbisi, Paul A.

AU - Ashley-Koch, Allison E.

AU - Austin, S. Bryn

AU - Avdibegovic, Esmina

AU - Babic, Dragan

AU - Baekvad-Hansen, Marie

AU - Baker, Dewleen G.

AU - Beckham, Jean C.

AU - Bierut, Laura J.

AU - Bisson, Jonathan I.

AU - Boks, Marco P.

AU - Bolger, Elizabeth A.

AU - Borglum, Anders D.

AU - Bradley, Bekh

AU - Brashear, Megan

AU - Breen, Gerome

AU - Bryant, Richard A.

AU - Bustamante, Angela C.

AU - Bybjerg-Grauholm, Jonas

AU - Calabrese, Joseph R.

AU - Rutten, Bart P. F.

AU - Schizophrenia Working Group of the Psychiatric Genomics Consortium

PY - 2019/5

Y1 - 2019/5

N2 - IMPORTANCE There is a well-established negative association of educational attainment (EA) and other traits related to cognitive ability with posttraumatic stress disorder (PTSD), but the underlying mechanisms are poorly understood.OBJECTIVES To investigate the association of PTSD with traits related to EA.DESIGN, SETTING, AND PARTICIPANTS Genetic correlation, polygenic risk scoring, and mendelian randomization (MR) were conducted including 23 185 individuals with PTSD and 151 309 control participants from the Psychiatric Genomics Consortium for PTSD and up to 1 131 881 individuals assessed for EA and related traits from UK Biobank, 23andMe, and the Social Science Genetic Association Consortium. Data were analyzed from July 3 through November 19, 2018.MAIN OUTCOMES AND MEASURES Genetic correlation obtained from linkage disequilibrium score regression, phenotypic variance explained by polygenic risk scores, and association estimates from MR.RESULTS Summary association data from multiple genome-wide association studies were available for a total of 1 180 352 participants (634 391 [53.7%] women). Posttraumatic stress disorder showed negative genetic correlations with EA (r(g) = -0.26; SE = 0.05; P = 4.60 x 10(-8)). Mendelian randomization analysis, conducting considering a random-effects inverse-variance weighted method, indicated that EA has a negative association with PTSD (beta = -0.23; 95% CI, -0.07 to -0.39; P = .004). Investigating potential mediators of the EA-PTSD association, propensity for trauma exposure and risk-taking behaviors were observed as risk factors for PTSD independent of EA (trauma exposure: beta = 0.37; 95% CI, 0.19 to 0.52; P = 2.57 x 10(-5); risk-taking: beta = 0.76; 95% CI, 0.38 to 1.13; P = 1.13 x 10(-4)), while income may mediate the association of EA with PSTD (MR income: beta = -0.18; 95% CI, -0.29 to -0.07; P =.001; MR EA: beta = -0.23; 95% CI, -0.39 to -0.07; P =.004; multivariable MR income: beta = -0.32; 95% CI, -0.57 to 0.07; P = .02; multivariable MR EA: beta = -0.04; 95% CI, -0.29 to 0.21; SE, 0.13; P = .79).CONCLUSIONS AND RELEVANCE Large-scale genomic data sets add further evidence to the negative association of EA with PTSD, also supporting the role of economic status as a mediator in the association observed.

AB - IMPORTANCE There is a well-established negative association of educational attainment (EA) and other traits related to cognitive ability with posttraumatic stress disorder (PTSD), but the underlying mechanisms are poorly understood.OBJECTIVES To investigate the association of PTSD with traits related to EA.DESIGN, SETTING, AND PARTICIPANTS Genetic correlation, polygenic risk scoring, and mendelian randomization (MR) were conducted including 23 185 individuals with PTSD and 151 309 control participants from the Psychiatric Genomics Consortium for PTSD and up to 1 131 881 individuals assessed for EA and related traits from UK Biobank, 23andMe, and the Social Science Genetic Association Consortium. Data were analyzed from July 3 through November 19, 2018.MAIN OUTCOMES AND MEASURES Genetic correlation obtained from linkage disequilibrium score regression, phenotypic variance explained by polygenic risk scores, and association estimates from MR.RESULTS Summary association data from multiple genome-wide association studies were available for a total of 1 180 352 participants (634 391 [53.7%] women). Posttraumatic stress disorder showed negative genetic correlations with EA (r(g) = -0.26; SE = 0.05; P = 4.60 x 10(-8)). Mendelian randomization analysis, conducting considering a random-effects inverse-variance weighted method, indicated that EA has a negative association with PTSD (beta = -0.23; 95% CI, -0.07 to -0.39; P = .004). Investigating potential mediators of the EA-PTSD association, propensity for trauma exposure and risk-taking behaviors were observed as risk factors for PTSD independent of EA (trauma exposure: beta = 0.37; 95% CI, 0.19 to 0.52; P = 2.57 x 10(-5); risk-taking: beta = 0.76; 95% CI, 0.38 to 1.13; P = 1.13 x 10(-4)), while income may mediate the association of EA with PSTD (MR income: beta = -0.18; 95% CI, -0.29 to -0.07; P =.001; MR EA: beta = -0.23; 95% CI, -0.39 to -0.07; P =.004; multivariable MR income: beta = -0.32; 95% CI, -0.57 to 0.07; P = .02; multivariable MR EA: beta = -0.04; 95% CI, -0.29 to 0.21; SE, 0.13; P = .79).CONCLUSIONS AND RELEVANCE Large-scale genomic data sets add further evidence to the negative association of EA with PTSD, also supporting the role of economic status as a mediator in the association observed.

KW - COGNITIVE-ABILITY

KW - GENETIC-VARIANTS

KW - RNA-SEQ

KW - RISK

KW - SCHIZOPHRENIA

KW - TRAJECTORIES

KW - DIVERSITY

KW - PTSD

U2 - 10.1001/jamanetworkopen.2019.3447

DO - 10.1001/jamanetworkopen.2019.3447

M3 - Article

C2 - 31050786

SN - 2574-3805

VL - 2

SP - 1

EP - 17

JO - Jama network open

JF - Jama network open

IS - 5

M1 - 193447

ER -