Identification of Novel Therapeutic Targets for Hypertension

Persistently high blood pressure remains the leading risk factor for mortality worldwide. This study aims to identify potential drug targets for hypertension.

Mendelian randomization was used to identify therapeutic targets for hypertension. Genome-wide association study summary statistics were obtained from the UK Biobank and FinnGen study. Cis-expression quantitative trait loci from the eQTLGen Consortium served as genetic instruments. Colocalization analysis evaluated the likelihood of shared causal variants between single-nucleotide polymorphisms influencing hypertension and gene expression. Survival analysis of UK Biobank data assessed hypertension and mortality risks across participants with different gene alleles.

Mendelian randomization analysis identified 190 drug targets in the discovery cohort and 65 in the replication cohort after multiple testing correction. Colocalization analysis identified 14 hypertension-related drug targets, including ACE, AIMP1, CDC25A, EHMT2, FES, GPX1, GRK4, HSD3B7, NEK4, PTPN12, SIK2, SLC22A4, SLC2A4, and TNFSF12. Survival analysis revealed individuals with the A allele at rs4308 in the ACE gene had a higher incidence of hypertension, while those with the T allele at rs11242109 in the SLC22A4 gene showed a lower hypertension-specific mortality rate.

Drug target Mendelian randomization studies offer new directions for hypertension treatment, providing insights into its mechanisms and robust targets for developing antihypertensive drugs.