Association of Economic Status and Educational Attainment With Posttraumatic Stress Disorder

Renato Polimanti,Rajendra A Morey,Caroline M Nievergelt,Karestan C Koenen,Adam X Maihofer,Dan J Stein,Joel Gelernter,Murray B Stein,Mark W Logue,Andrew Ratanatharathorn,Karmel W Choi

doi:10.1001/jamanetworkopen.2019.3447

Abstract

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. To investigate the association of PTSD with traits related to EA. 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. Genetic correlation obtained from linkage disequilibrium score regression, phenotypic variance explained by polygenic risk scores, and association estimates from MR. 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 (rg = -0.26; SE = 0.05; P = 4.60 × 10-8). Mendelian randomization analysis, conducting considering a random-effects inverse-variance weighted method, indicated that EA has a negative association with PTSD (β = -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: β = 0.37; 95% CI, 0.19 to 0.52; P = 2.57 × 10-5; risk-taking: β = 0.76; 95% CI, 0.38 to 1.13; P = 1.13 × 10-4), while income may mediate the association of EA with PSTD (MR income: β = -0.18; 95% CI, -0.29 to -0.07; P = .001; MR EA: β = -0.23; 95% CI, -0.39 to -0.07; P = .004; multivariable MR income: β = -0.32; 95% CI, -0.57 to 0.07; P = .02; multivariable MR EA: β = -0.04; 95% CI, -0.29 to 0.21; SE, 0.13; P = .79). 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.

Highlights

Posttraumatic stress disorder (PTSD) is a psychological condition that occurs in some individuals after exposure to a major traumatic event
Mendelian randomization analysis, conducting considering a random-effects inverse-variance weighted method, indicated that educational attainment (EA) has a negative association with posttraumatic stress disorder (PTSD) (β = −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, while income may mediate the association of EA with PSTD (MR income: β = −0.18; 95% CI, −0.29 to −0.07; P = .001; mendelian randomization (MR) EA: β = −0.23; 95% CI, −0.39 to −0.07; P = .004; multivariable MR income: β = −0.32; 95% CI, −0.57 to 0.07; P = .02; multivariable MR EA: β = −0.04; 95% CI, −0.29 to 0.21; SE, 0.13; P = .79)

Summary

Introduction

Posttraumatic stress disorder (PTSD) is a psychological condition that occurs in some individuals after exposure to a major traumatic event. Prospective studies have suggested that many variables previously considered outcomes of trauma are likely to be pretrauma risk factors.[1] Among these complex associations, that of PTSD with cognitive ability and educational attainment (EA; ie, the number of years of schooling that individuals complete) is among the most puzzling. Powered genome-wide association studies (GWASs) are able to dissect the predisposition to complex traits This requires extremely large sample sizes to detect the polygenic architecture of complex traits, overcoming their heterogeneity to have sufficient power to find risk loci of very small effect.[9] By combining such small-effect loci, it is possible to build genetic instruments that can be used to investigate complex epidemiological associations, such as the underlying mechanisms connecting PTSD, traits related to EA, and the potential mediation of other pretrauma risk factors. Genetic variants are allocated at conception and do not change throughout life, and they can be used to define reliable genetic instruments that can be applied in a mendelian randomization (MR) analysis.[10,11,12,13,14] The basic principle in MR is that an instrumental variable based on genetic variants associated with a phenotype can be used to represent, or mirror, the disease risk associated with that phenotype without the presence of possible environmental confounders.[15]

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