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 (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). 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.
