高血压与帕金森病的共享基因位点识别研究

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【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 【中图分类号】 R742.5 R544.1 【文献标识码】 AD0I：10.12114/j.issn.1007-9572.2024.0583

【Abstract】BackgroundHypertension （HT）and Parkinson's disease （PD）have shown comorbidity in observational studies，buttheirshared geneticbasisandcausalrelationshipsremainunclear.ObjectiveThisstudyutilizedlarge-scale genome-wideasociationstudies （GWAS）summarydatatoinvestigatethesharedgeneticetiologyandcausalrelationshipsbetwen HTandPD.MethodsGWAS summarydata was extracted fromtheR5releaseof theFinnGen consortium （2162Parkinson's disease patientsand216630controls）andthesummarydata fromtheUK Biobank （including129909hypertension patientsand 354 689controls）andohovalladocalgeneticorratiossssdusinglgedsqlisreregesso） and local genetic heritability estimation （ p -HESS）. Cross-trait Meta-analysis was used to identify pleiotropic single nucleotide polymorphisms （SNPs）shared between HTand PD，and bidirectional Mendelian randomization （MR）analysis was performed to inferpotentialcausalrelationships.ResultsGeneticcorelationanalysisrevealednosignificantoverallcorelationbetweenHT and PD （ =0.067， P =0.527）.Local analysis identified three marginally significant regions （ P <0.05），but none reached statistical ′g  significanceafterBonferronicorection（P>0.05）.Cross-trait Meta-analysisconfirmd37significantSNPsassociaed withoth HT and PD. Bidirectional MR analysis demonstrated a significant causal effect of HTon 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）.Sensitivityanalyses further validated the robustnessoftheresults.ConclusionThisstudyfoundthathypertensionisariskfactorforParkinson'sdisease，andthereisa commongeneticbasisandcausalrelationshipbetweenthetwo.Theidentificationofsharedgeneticlociisofgreatsignificance in disease prevention and treatment strategies.

【Key words】Hypertension; Parkinson's disease; Genetic correlation; Cross-trait meta-analysis;Mendelian randomization

帕金森病（Parkinson'sdisease，PD）是一种常见的神经退行性疾病，主要表现为震颤、僵硬、运动迟缓和姿势不稳等运动症状。（剩余11033字）