Genetic predisposition to Parkinson's disease and risk of cardio and cerebrovascular disease: a Mendelian randomization study

Wang, Mengmeng; Zhang, Zhizhong; Liu, Dandan; Ji, Lei; Huang, Shuangjiao; Cao, Liping; Wei, Ning; Ye, Dan; Ma, Yazhou; Lian, Xuegan

doi:10.1016/j.parkreldis.2021.11.021

Cited by 6 publications

(6 citation statements)

References 28 publications

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“…The MR-PRESSO method was applied to detect horizontal pleiotropy and correct it via outlier removal [ 27 ]. To determine whether our assessment results were driven by specific SNPs with a significant impact, the leave-one-out sensitivity analysis was performed, removing one SNP in turn and performing the IVW method on the remaining SNPs [ 33 ]. We scanned each SNP for its potential secondary phenotypes using the GWAS catalog ( (accessed on 15 July 2022)) and excluded the SNPs associated with traits other than hip OA ( Table S1 ), and performed the relevant MR analyses again.…”

Section: Methodsmentioning

confidence: 99%

Hip Osteoarthritis and the Risk of Lacunar Stroke: A Two-Sample Mendelian Randomization Study

Shen

Cao

et al. 2022

Genes

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Whether hip osteoarthritis (OA) could increase the risk of lacunar stroke (LS) is not well understood. This two-sample Mendelian randomization (MR) study aimed to investigate in depth the effect of genetically predicted hip OA on LS risk. Hip OA-related instrumental variables (IVs) were selected from a genome-wide association study (GWAS) of 393,873 individuals. The summary data of LS were obtained from a GWAS meta-analysis, including 16,030 cases and 248,929 controls. We used the inverse-variance weighted (IVW) as the primary MR analysis method. Moreover, the weighted-median, MR-Egger regression, and the MR pleiotropy residual sum and outlier (MR-PRESSO) test were supplementary methods. The sensitivity analysis was performed using the leave-one-out test. We identified the positive causal relationship between hip OA and the risk of LS (odds ratio [OR] = 1.20, 95% confidence interval [CI]: 1.07, 1.36; p = 0.002 using the IVW method). The weighted median method provided similar results. There was no evidence of directed pleiotropy, and sensitivity analysis results were stable, suggesting the robustness of our study. This study showed a causal effect of hip OA on the risk of LS, and more efforts should be made to explore the potential mechanisms in the future.

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Section: Methodsmentioning

confidence: 99%

Hip Osteoarthritis and the Risk of Lacunar Stroke: A Two-Sample Mendelian Randomization Study

Shen

Cao

et al. 2022

Genes

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“…Orthostatic hypotension has been shown to increase the risk of stroke 10.3389/fnins.2022.995045 (Eigenbrodt et al, 2000;Mehta et al, 2019). Wang et al proposed that atrial fibrillation might be another potential mechanism of PD on the risk of stroke (Wang et al, 2022; Supplementary Figure 1). Although the above explanations are biologically plausible, more well-designed explorations are still needed to confirm the exact mechanisms of the causal effect of PD on stroke risk.…”

Section: Discussionmentioning

confidence: 99%

“…Huang et al performed a follow-up study and proposed that there was a significantly increased risk of IS in PD patients ( Huang et al, 2013 ). So far, two MR studies have suggested that PD is causally affected by the risk of IS in European populations ( Fang et al, 2022 ; Wang et al, 2022 ). Similar to their findings, our present study also identified the causal effects of PD on the risk of IS.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, our present study discovered the causal relationship between PD and stroke and explored the potential genetic effect of PD on the risk of ICH, which has not been reported before. Besides, by comparison with Mengmeng Wang’s article ( Wang et al, 2022 ), we added another sensitivity analysis to this study. After removing the SNPs associated with PD-related secondary phenotypes based on the PhenoScanner website, the secondary MR-analysis’s results repeated our initial ones, making our findings more credible.…”

Section: Discussionmentioning

confidence: 99%

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Genetic predisposition to neurodegenerative diseases and risk of stroke: A Mendelian randomization study

Wang

Hou³

et al. 2022

Front. Neurosci.

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BackgroundTraditional epidemiological studies suggested that Neurodegenerative diseases (ND) might correlate with stroke. We intend to explore whether the two most common neurodegenerative diseases [Alzheimer’s disease (AD) and Parkinson’s disease (PD)] are causally associated with stroke and its subtypes.MethodsTwo-sample Mendelian Randomization (MR) method was used to explore the causal relationships. Candidate genetic instrumental variables (IVs) for AD and PD were collected from the genome-wide association studies (GWAS) in European populations. The inverse-variance weighted (IVW) method was the primary method of MR analysis, and the weighted median method was supplementary. In addition, the MR-Egger method and the MR-PRESSO test were used as well.ResultsWe found no causal effects of AD on stroke, Ischemic stroke (IS), or Intracerebral hemorrhage (ICH). As for PD and stroke, our preliminary results showed PD could causally influence the risk of stroke [odds ratio (OR): 1.04; 95% confidence interval (CI): 1.02–1.07; P = 0.001 by the IVW method], although the alternative method did not support this result. We identified the positive causal relationship between PD and the risk of IS (OR = 1.04; 95% CI: 1.02–1.07; P = 0.001 by the IVW method), and the alternative MR methods produced similar results. The present study found there was no causal relationship between PD and ICH.ConclusionThis study found a causal relationship between genetic susceptibility to PD and the incidence of stroke (especially IS) in the European population; however, there was no causal relation between AD and stroke risk.

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“…However, there are few studies on the association between PD and VTE. Although a Mendelian randomization (MR) analysis explored no significant association between PD and MI [15], it was different from the results of most of the observational studies, and it used a European population for the PD dataset but a mixed population for the MI dataset. Unlike their study, the PD and MI datasets we have chosen were all from European populations, and the MI dataset we have chosen has a larger sample size.…”

Section: Introductionmentioning

confidence: 99%

Causal Relationship between Parkinson’s Disease with Heart and Vascular Disease: A Two-Sample Mendelian Randomization Study

Chen,

Zhang,

et al. 2024

Eur Neurol

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Introduction: The aim of this study was to investigate the causal relationship between Parkinson’s disease (PD) and myocardial infarction (MI), atrial fibrillation and flutter (AF), and venous thromboembolism (VTE) by Mendelian randomization (MR) analysis. Methods: By using data from publicly available genome-wide association studies from databases, single nucleotide polymorphisms were screened as instrumental variables, and the MR analysis was finished by inverse-variance weighted (IVW), MR-egger, weighted median methods. Results: The primary IVW method showed a negative association between genetically predicted PD and risk of MI (OR = 0.9989; 95% CI: 0.9980–0.9998; p = 0.02). However, PD was not significantly associated with AF or VTE. Conclusion: This study suggests a negative association between PD with MI, which implies that PD has a protective effect on MI.

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Genetic predisposition to Parkinson's disease and risk of cardio and cerebrovascular disease: a Mendelian randomization study

Cited by 6 publications

References 28 publications

Hip Osteoarthritis and the Risk of Lacunar Stroke: A Two-Sample Mendelian Randomization Study

Hip Osteoarthritis and the Risk of Lacunar Stroke: A Two-Sample Mendelian Randomization Study

Genetic predisposition to neurodegenerative diseases and risk of stroke: A Mendelian randomization study

Causal Relationship between Parkinson’s Disease with Heart and Vascular Disease: A Two-Sample Mendelian Randomization Study

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