Obesity and hypertension mediate the effect of education on deep intracerebral hemorrhage: A Mendelian randomization study.

ABSTRACT

BACKGROUND: Educational attainment (EA) as a stable indicator of socioeconomic status has been confirmed to affect intracerebral hemorrhage (ICH), but the mechanism relating EA and ICH is still unknown. AIM: To explore the causal relationship between EA and ICH through a bidirectional and two-step Mendelian randomization (MR) study. METHODS: Using summary-level Genome-wide Association Study using GWAS data FROM CASES AND CONTROLS of European ancestry, we performed bidirectional and two-step MR analyses to explore the causal relationship between educational attainment and ICH to understand the mediating influence of risk factors in this process. We also carried out subgroup analysis according to the different sites (deep and lobar) of ICH. A set of sensitivity analyses were performed to test valid MR assumptions. RESULTS: Bidirectional MR analysis consistently demonstrated a unidirectional causal effect, revealing that higher EA had a protective influence on ICH. Each additional 1-standard deviation (SD) increase in genetically predicted years of schooling was associated with a reduced risk of all ICH (inverse variance weighted (IVW) OR 0.381 [95 %CI 0.264-0.549]), deep ICH (OR 0.334 [95 %CI 0.216-0.517]), and lobar ICH (OR 0.422 [95 %CI 0.261-0.682]). The mediating effect of EA on all ICH was mediated via systolic blood pressure (SBP) (6.93 % [1.20-13.45 %]) and body mass index (BMI) (17.87 % [3.92-34.64 %]), and the mediating effect of EA on deep ICH was also mediated via SBP (7.85 % [1.55-15.07 %]) and BMI (18.63 % [4.02-36.26 %]). CONCLUSION: This study provides robust genetic evidence for supporting the protective effect of EA on ICH risk, with further evidence that the effect of EA on deep ICH is partially mediated through hypertension and obesity. Further validation is needed to ascertain whether these findings are applicable to other racial or general population groups.