Hypertension (HT) and Parkinson's disease (PD) have shown comorbidity in observational studies, but their shared genetic basis and causal relationships remain unclear.

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.

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.

Genetic correlation analysis revealed no significant overall correlation between HT and PD (r_g=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.

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.

高血压与帕金森病在观察性研究中已经表现出共病现象，但其共同遗传基础和因果关系尚未明确。

本研究利用大规模全基因组关联研究（GWAS）的汇总数据，探讨高血压与帕金森病的共同遗传病因及因果关系。

提取FinnGen项目R5版本中GWAS汇总统计数据（2 162例帕金森病患者和216 630例对照）和英国生物银行的汇总统计数据（包含129 909例高血压患者和354 689例对照），通过连锁不平衡得分回归（LDSC）和局部遗传力估计（ρ-HESS）评估整体和局部的遗传相关性。采用跨性状Meta分析揭示高血压与帕金森病共享的多效性基因组单核苷酸多态性（SNPs），并通过双向孟德尔随机化（MR）分析推断潜在的因果关系。

遗传相关性分析显示，高血压与帕金森病之间未观察到整体相关性（r_g=0.067，P=0.527）。局部分析识别出3个边缘显著区域（P<0.05），但在Bonferroni校正后无统计学意义（P>0.05）。跨性状Meta分析确认了37个与高血压和帕金森病相关的SNPs。双向MR分析结果表明，高血压对帕金森病具有因果效应（β=0.655，SE=0.278，P=0.019），而帕金森病对高血压无反向因果效应（β=0.002，SE=0.001，P=0.179）。敏感性分析进一步验证了结果的稳健性。

本研究发现高血压是帕金森病的危险因素，两者之间存在共同遗传基础和因果关系，共享遗传位点的识别在疾病预防和治疗策略中具有重要意义。