高血压与帕金森病的共享基因位点识别研究

doi:10.12114/j.issn.1007-9572.2024.0583

中国全科医学 ›› 2026, Vol. 29 ›› Issue (02): 201-206.DOI: 10.12114/j.issn.1007-9572.2024.0583

• 论著 • 上一篇

高血压与帕金森病的共享基因位点识别研究

周文超¹^,², 梁佳琪¹^,², 姚尚满³, 薛朝¹^,², 刘龙¹^,²^,^*(), 郭相杰¹^,⁴^,⁵^,^*()

1．030001　山西省太原市，山西医科大学医学科学院
2．030001　山西省太原市，山西医科大学公共卫生学院
3．030001　山西省太原市，山西医科大学健康人文研究中心
4．030001　山西省太原市，山西医科大学转化医学中心
5．030600　山西省晋中市，山西医科大学法医学院

收稿日期:2024-12-10 修回日期:2025-02-20 出版日期:2026-01-15 发布日期:2025-12-11
通讯作者: 刘龙, 郭相杰
作者贡献：
周文超、郭相杰提出研究思路，负责最终版本修订，对论文负责；周文超负责统计学分析、绘制图表、论文起草；梁佳琪、薛朝负责数据收集、采集、清洗；姚尚满负责图表的优化；刘龙设计研究方案。
基金资助:
国家自然科学基金资助项目(82271925); 山西省基础研究计划资助项目(20210302123314); 山西省研究生教育创新计划资助项目(2024SJ219)

Identification of Shared Loci between Hypertension and Parkinson's Disease

ZHOU Wenchao¹^,², LIANG Jiaqi¹^,², YAO Shangman³, XUE Zhao¹^,², LIU Long¹^,²^,^*(), GUO Xiangjie¹^,⁴^,⁵^,^*()

1. Academy of Medical Sciences, Shanxi Medical University, Taiyuan 030001, China
2. School of Public Health, Shanxi Medical University, Taiyuan 030001, China
3. Health Humanities Research Center, Shanxi Medical University, Taiyuan 030001, China
4. Translational Medicine Research Center, Shanxi Medical University, Taiyuan 030001, China
5. School of Forensic Medicine, Shanxi Medical University, Jinzhong 030600, China

Received:2024-12-10 Revised:2025-02-20 Published:2026-01-15 Online:2025-12-11
Contact: LIU Long, GUO Xiangjie

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摘要/Abstract

摘要： 背景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。目的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。方法提取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。结果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（rg=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。结论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。

关键词: 高血压, 帕金森病, 遗传相关性, 跨性状Meta分析, 孟德尔随机化

Abstract:

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 (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.

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.

Key words: Hypertension, Parkinson's disease, Genetic correlation, Cross-trait meta-analysis, Mendelian randomization

中图分类号:

R 742.5　R 544.1

周文超,梁佳琪,姚尚满,等. 高血压与帕金森病的共享基因位点识别研究[J]. 中国全科医学, 2026, 29(02): 201-206. DOI: 10.12114/j.issn.1007-9572.2024.0583.
ZHOU Wenchao,LIANG Jiaqi,YAO Shangman, et al. Identification of Shared Loci between Hypertension and Parkinson's Disease[J]. Chinese General Practice, 2026, 29(02): 201-206. DOI: 10.12114/j.issn.1007-9572.2024.0583.

图/表 8

参考文献 25

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疾病	病例数（例）	对照数（例）	来源	样本总数（例）
帕金森病	2 162	216 630	欧洲	218 792
高血压	129 909	354 689	欧洲	484 598

疾病	病例数（例）	对照数（例）	来源	样本总数（例）
帕金森病	2 162	216 630	欧洲	218 792
高血压	129 909	354 689	欧洲	484 598

染色体	起始	终止	SNPs数量（个）	R²	P值	包含基因
4	14272001	15147446	1 689	-1.83×10^-4	0.035	CPEB2
6	132765669	134244243	2 448	-2.00×10^-4	0.040	TAAR1
11	63804569	65898631	2 172	2.26×10^-4	0.023	STIP1

染色体	起始	终止	SNPs数量（个）	R²	P值	包含基因
4	14272001	15147446	1 689	-1.83×10^-4	0.035	CPEB2
6	132765669	134244243	2 448	-2.00×10^-4	0.040	TAAR1
11	63804569	65898631	2 172	2.26×10^-4	0.023	STIP1

SNPs	染色体	位置	A1	A2	P₁值	P₂值	P_meta值	基因
rs4712653	6	22125964	T	C	3.36×10^-4	4.91×10^-10	8.72×10^-10	CASC15
rs4712656	6	22136262	G	C	3.64×10^-4	1.41×10^-11	2.62×10^-11	CASC15
rs6911827	6	22130601	C	T	4.40×10^-4	2.56×10^-11	4.68×10^-11	CASC15
rs6915322	6	22136160	C	T	3.49×10^-4	9.38×10^-12	1.76×10^-11	CASC15
rs7768871	6	22109189	C	T	3.33×10^-4	9.72×10^-11	1.77×10^-10	CASC15
rs9368402	6	22125157	C	T	2.10×10^-4	5.93×10^-11	1.11×10^-11	CASC15
rs10957776	8	76754263	A	C	4.25×10^-9	9.51×10^-4	6.99×10^-9	None
rs2920919	8	76712697	A	G	8.15×10^-4	3.02×10^-9	5.03×10^-9	None
rs2920920	8	76711428	G	A	8.15×10^-4	2.71×10^-9	4.53×10^-9	None
rs2920921	8	76708796	A	G	8.15×10^-4	2.79×10^-9	4.65×10^-9	None
rs2920930	8	76733973	T	G	9.42×10^-4	4.77×10^-9	7.85×10^-9	None
rs2920932	8	76739943	T	A	9.51×10^-4	6.17×10^-9	1.01×10^-8	None
rs2977321	8	76721610	C	T	9.15×10^-4	4.77×10^-9	7.87×10^-9	None
rs2977324	8	76716737	T	G	8.47×10^-4	2.34×10^-9	3.90×10^-9	None
rs2977345	8	76725867	T	C	8.98×10^-4	4.91×10^-9	8.09×10^-9	None
rs7000794	8	76745880	A	G	5.20×10^-9	9.60×10^-4	8.53×10^-9	None
rs72663572	8	76761846	G	A	4.82×10^-9	9.42×10^-4	7.92×10^-9	None
rs11105337	12	89993507	A	T	8.50×10^-40	3.38×10^-4	2.01×10^-39	ATP2B1
rs11105352	12	90026462	G	A	2.37×10^-41	6.61×10^-41	5.45×10^-41	ATP2B1
rs11105353	12	90026463	C	A	2.37×10^-41	6.61×10^-41	5.45×10^-41	ATP2B1
rs11105354	12	90026523	A	G	6.74×10^-41	6.22×10^-4	1.54×10^-40	ATP2B1
rs11105364	12	90069276	T	G	1.21×10^-40	6.16×10^-4	2.75×10^-40	ATP2B1
rs11105368	12	90074441	G	C	1.25×10^-40	6.16×10^-4	2.84×10^-40	ATP2B1
rs11105375	12	90088580	T	A	7.46×10^-39	6.09×10^-4	1.67×10^-38	ATP2B1
rs11105378	12	90090741	C	T	5.97×10^-39	6.13×10^-4	1.34×10^-38	ATP2B1
rs111478946	12	90058842	G	A	1.27×10^-40	6.40×10^-4	2.88×10^-40	ATP2B1
rs117742247	12	89991313	C	T	1.31×10^-36	5.27×10^-4	2.92×10^-36	ATP2B1
rs12579302	12	90050503	A	G	1.11×10^-40	6.57×10^-4	2.52×10^-40	ATP2B1
rs17249754	12	90060586	G	A	5.86×10^-41	6.20×10^-4	1.33×10^-40	ATP2B1
rs2681472	12	90008959	A	G	4.53×10^-41	6.31×10^-4	1.03×10^-40	ATP2B1
rs2681492	12	90013089	T	C	1.44×10^-41	5.34×10^-4	3.32×10^-41	ATP2B1
rs4842675	12	90075243	C	T	1.32×10^-40	6.16×10^-4	3.00×10^-40	ATP2B1
rs57481061	12	90019178	C	G	1.16×10^-37	5.09×10^-4	2.59×10^-37	ATP2B1
rs6538195	12	90062376	G	A	4.63×10^-41	6.16×10^-4	1.05×10^-40	ATP2B1
rs73437338	12	90054619	T	C	2.88×10^-38	6.18×10^-4	6.36×10^-38	ATP2B1
rs73437358	12	90072076	G	A	5.39×10^-41	6.16×10^-4	1.23×10^-40	ATP2B1
rs12579052	12	90132147	G	A	1.50×10^-17	9.39×10^-4	2.68×10^-17	LOC107984543

高血压与帕金森病的共享基因位点识别研究

Identification of Shared Loci between Hypertension and Parkinson's Disease

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参考文献 25

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方向	方法	SNPs数量（个）	OR（95%CI）	β	SE	P值
高血压→帕金森病	Inverse variance weighted	388	1.924（1.116~3.318）	0.655	0.278	0.019
	MR-Egger		1.895（0.440~8.149）	0.639	0.744	0.391
	Weighted median		1.230（0.517~2.929）	0.207	0.443	0.640
帕金森病→高血压	Inverse variance weighted	16	1.002（0.999~1.004）	0.002	0.001	0.179
	MR-Egger		1.003（0.997~1.009）	0.003	0.003	0.381
	Weighted median		1.001（0.997~1.005）	0.001	0.002	0.591

方向	Q	df	P值
高血压→帕金森病	412	388	0.194
帕金森病→高血压	13.1	15	0.598

方向	Egger_intercept	SE	P值
高血压→帕金森病	1.29×10^-4	5.77×10^-3	9.82×10^-1
帕金森病→高血压	-2.81×10^-4	7.50×10^-4	7.14×10^-1

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