Genetically predicted ZDHHC7 expression was associated with a reduced risk of hypertension (OR 0.995; 95% CI 0.992-0.998; P<0.001).
Observational (n=484,598)
Does genetic predisposition to higher ZDHHC7 expression reduce the risk of hypertension in European populations?
Genetic evidence suggests that increased ZDHHC7 expression may reduce the risk of hypertension, potentially mediated by specific immune cells and plasma metabolites.
Odds Ratio: 0.995 (95% CI 0.992–0.998)
p-value: p=<0.001
Abstract Objective To investigate the specific mechanisms by which zinc finger DHHC-type containing 7 (ZDHHC7) regulates immune cells and plasma metabolites to reduce the risk of hypertension. Methods Expression quantitative trait loci (eQTL) data for ZDHHC7 were obtained from the eQTLGen database (n = 26,118), while genome-wide association studies (GWAS) data for hypertension (n = 484,598), immune cells (n = 3658), and plasma metabolites (n = 8192) were extracted from the GWAS Catalog. All datasets were derived from European populations. Five Mendelian randomization (MR) methods, including inverse variance weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode, were used to evaluate causal relationships. Sensitivity analyses were performed using Cochran’s Q test, MR-Egger intercept, leave-one-out analysis, and MR-PRESSO. Statistical power of the MR analysis was assessed via post hoc power calculation. Two-step MR was conducted to evaluate the mediating effects of immune cells and plasma metabolites on the relationship between ZDHHC7 and hypertension risk. Results All 5 MR methods indicated a negative association between ZDHHC7 and hypertension risk (IVW: OR = 0.995, 95% CI, 0.992-0.998, P .001; MR-Egger: OR = 0.994, 95% CI, 0.989-0.998, P = .014; weighted median: OR = 0.994, 95% CI, 0.991-0.998, P = .004; simple mode: OR = 0.993, 95% CI, 0.987-1.000, P = .049; weighted mode: OR = 0.994, 95% CI, 0.990-0.997, P .001). The summary-level Mendelian randomization (SMR) analysis yielded consistent results (OR = 0.995, 95% CI, 0.990-0.998, P = .011). Sensitivity analyses showed no significant heterogeneity or bias. The estimated post hoc power was 23.73%. Mediation analysis further revealed that 3 immune cell phenotypes (the proportion of B cell subsets lacking IgD and CD27 markers, expression of CD123 on plasmacytoid dendritic cells, and expression of CD123 on CD62L+ plasmacytoid dendritic cells) and 3 plasma metabolites (1-stearoylphosphatidylinositol, nicotinic acid, and lactate) mediated the relationship between ZDHHC7 and hypertension risk. Conclusion ZDHHC7 may reduce the risk of hypertension by modulating specific immune cells and plasma metabolites.
Meijuan et al. (Tue,) conducted a observational in Hypertension (n=484,598). ZDHHC7 expression was evaluated on Hypertension risk (OR 0.995, 95% CI 0.992-0.998, p=<0.001). Genetically predicted ZDHHC7 expression was associated with a reduced risk of hypertension (OR 0.995; 95% CI 0.992-0.998; P<0.001).