Mendelian randomization analysis of causal association between psychobehavioral factors and essential hypertension or blood pressure levels

LI Zekun; MA Xiao; YANG Junti; ZHANG Wei

doi:10.3969/j.issn.2097-1753.2025.05.017

Abstract：Objective To evaluate the causal association between psychobehavioral factors and essential hypertension or blood pressure using the Mendelian randomization(MR)method.Methods Single nucleotide polymorphism(SNP)strongly associated with eight psychobehavioral factors(depression,mood disorder,personality disorder,schizophrenia,dementia,substance abuse,sleep disorders,and alcohol dependence)were retrieved as instrumental variables from human genome-wide association studies.A two-sample Mendelian randomization analysis was conducted to assess the causal association between the eight psychobehavioral factors and essential hypertension,systolic blood pressure,and diastolic blood pressure using the random-effects inverse-variance weighted(IVW)method,MR-Egger method,and MR-PRESSO method.Cochran's Q test and MR-Egger intercept test were used to evaluate the heterogeneity and horizontal pleiotropy of the instrumental variable SNPs.Results The IVW model showed that sleep disorders were a risk factor for essential hypertension(OR=1.027,95％CI=1.015-1.039),and also a contributor to increased systolic blood pressure(β=0.543,95％CI=0.110-0.976)and diastolic blood pressure(β=0.796,95％CI=0.486-1.106).Dementia also contributed to increased systolic blood pressure(β=0.228,95％CI=0.093-0.363)and diastolic blood pressure(β=0.169,95％CI=0.001-0.337),but was not associated with an increased risk of essential hypertension(P＞0.05).No causal association was observed between other psychobehavioral factors and essential hypertension,systolic blood pressure,or diastolic blood pressure(all P＞0.05).The results of MR-Egger and MR-PRESSO aligned with those of IVW.Cochran's Q test indicated that there was heterogeneity among SNP in the causal association of sleep disorders with essential hypertension and diastolic blood pressure(Q=53.102,33.106,P=0.001,0.011),as well as in the causal association of dementia with diastolic blood pressure(Q=23.529,P=0.036).No heterogeneity was found among SNP in the causal association of sleep disorders and dementia with systolic blood pressure(both P＞0.05).MR-Egger intercept test showed no significant genetic-level pleiotropy(all P＞0.05).Conclusion Among the eight psychobehavioral factors,only sleep disorder are a risk factor for essential hypertension and elevated blood pressure at the genetic level.