Identification of Shared Loci between Hypertension and Parkinson's Disease
摘要
Background Hypertension (HT) and Parkinson's disease (PD) have shown comorbidity in observational studies, but their shared genetic basis and causal relationships remain unclear. Objective This study utilized large-scale genome-wide association studies (GWAS) summary data to investigate the shared genetic etiology and causal relationships between HT and PD. Methods GWAS summary data was extracted from the R5 release of the FinnGen consortium (2 162 Parkinson's disease patients and 216 630 controls) and the summary data from the UK Biobank (including 129 909 hypertension patients and 354 689 controls), and both overall and local genetic correlations was assessed using linkage disequilibrium score regression (LDSC) and local genetic heritability estimation (ρ-HESS). Cross-trait Meta-analysis was used to identify pleiotropic single nucleotide polymorphisms (SNPs) shared between HT and PD, and bidirectional Mendelian randomization (MR) analysis was performed to infer potential causal relationships. Results Genetic correlation analysis revealed no significant overall correlation between HT and PD (rg=0.067, P=0.527). Local analysis identified three marginally significant regions (P<0.05), but none reached statistical significance after Bonferroni correction (P>0.05). Cross-trait Meta-analysis confirmed 37 significant SNPs associated with both HT and PD. Bidirectional MR analysis demonstrated a significant causal effect of HT on PD (β=0.655, SE=0.278, P=0.019), while the reverse causal effect of PD on HT was not significant (β=0.002, SE=0.001, P=0.179). Sensitivity analyses further validated the robustness of the results. Conclusion This study found that hypertension is a risk factor for Parkinson's disease, and there is a common genetic basis and causal relationship between the two. The identification of shared genetic loci is of great significance in disease prevention and treatment strategies.