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Economic status mediates the relationship between educational attainment and posttraumatic stress disorder: a multivariable Mendelian randomization study

By Renato Polimanti, Andrew Ratanatharathorn, Adam X. Maihofer, Karmel Choi, Murray B Stein, Rajendra A. Morey, Mark W Logue, Caroline M. Nievergelt, Dan J. Stein, Karestan C. Koenen, Joel Gelernter, the Psychiatric Genomics Consortium Posttraumatic Stress Disorder Workgroup

Posted 21 Dec 2018
bioRxiv DOI: 10.1101/503300

Objectives: To investigate the genetic overlap and causal relationship between posttraumatic stress disorder (PTSD) and traits related to educational attainment. Design: Genetic correlation, polygenic risk scoring, and causal inference via multivariable Mendelian randomization (MR). Setting: Psychiatric Genomics Consortium for PTSD, UK Biobank, 23andMe, and Social Science Genetic Association Consortium. Participants: 23,185 PTSD cases and 151,309 controls; up to 1,131,881 individuals assessed for educational attainment and related traits. Main outcome measures: Genetic correlation obtained from linkage disequilibrium score regression, phenotypic variance explained by polygenic risk scores, and casual effects (beta values) estimated with MR. Results: PTSD showed strong negative genetic correlations with educational attainment (EdAtt; rg=−0.26, p=4.6x10−8). PRS based on genome-wide significant variants associated with EdAtt significantly predicted PTSD (p=6.16x10−4), but PRS based on variants associated with PTSD did not predict EdAtt (p>0.05). MR analysis indicated that EdAtt has negative causal effects on PTSD (beta=−0.23, p=0.004). Investigating potential mediators of the EdAtt-PTSD relationship, we observed that propensity for trauma exposure and risk-taking behaviors are risk factors for PTSD independently from EdAtt (beta = 0.36, p = 2.57x10−5 and beta = 0.76, p = 6.75x10−4, respectively), while income fully mediates the causal effect of EdAtt on PSTD (MR: Income beta = −0.18, p =0.001; EdAtt beta =−0.23, p=0.004; multivariable MR: Income beta = −0.32, p = 0.017; EdAtt beta = −0.04, p = 0.786). Conclusions: We report novel findings based on large-scale datasets regarding the relationship between educational attainment and PTSD, supporting the role of economic status as the key mediator in the causal relationship observed.

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