Elucidating the interplay between prostate cancer, education, and fat intake through causal inference and mediation analysis

Abstract Objective To disentangle the casual relationship between education and prostatic diseases and identify the potential pathways for these causal effects. Methods We performed a two-sample Mendelian randomization (MR) analysis to estimate the causal effects of education on prostatic diseases. To distinguish causality from genetic correlation and linkage disequilibrium, linkage disequilibrium score regression (LDSC) and colocalization analyses were implemented. We further investigated whether diet composition and obesity mediated the effect of education on prostate diseases. Results Our findings identified a significant adverse effect of higher education on prostate cancer risk that ORs were 1.20 (P = 9.0 × 10− 5) and the combined effects of two independent data were statistically significant (P = 4.5 × 10− 2). We also found suggestive evidence for a protective effect of higher education on prostatitis although the combined effects were not significant (P = 0.57). Additional genetic correlation and colocalization analyses reinforced these causal evidences. Further mediation analysis indicated that fat intake in diet composition and hip circumference in obesity partially mediated the effect of education on prostate cancer, with mediated proportions of 16.6% and 14.0%, respectively. Conclusion Higher educational attainment posed detrimental effect on prostate cancer, partly mediated by relative fat intake and hip circumference.