No genetic link between Parkinson's disease and SARS-CoV-2 infection: a two-sample Mendelian randomization study

Abstract

Objective: Existing literature has not clearly elucidated whether SARS-CoV-2 infection increases the incidence of Parkinson's disease or if Parkinson's disease patients are more susceptible to the effects of SARS-CoV-2 infection. To clarify the issue, this study employs a genetic epidemiological approach to investigate the association.

Methods: This study utilizes a two-sample Mendelian randomization analysis. The primary analysis employs the inverse variance-weighted (IVW) method, supplemented by secondary analyses including MR-Egger regression, weighted median, IVW radial method, and weighted mode, to evaluate the bidirectional causal relationship between Parkinson's disease and SARS-CoV-2 infection.

Results: IVW results showed no genetic causality between SARS-CoV-2 susceptibility, hospitalization rate and severity and Parkinson's disease. (IVW method: p = 0.408 OR = 1.10 95% CI: 0.87 ~ 1.39; p = 0.744 OR = 1.11 95% CI: 0.94 ~ 1.09; p = 0.436 OR = 1.05 95% CI: 0.93 ~ 1.17). Parkinson's disease was not genetically associated with susceptibility to new crown infections, hospitalization rates, and severity (IVW method: p = 0.173 OR = 1.01 95% CI: 0.99 ~ 1.03; p = 0.109 OR = 1.05 95% CI: 0.99 ~ 1.12; p = 0.209 OR = 1.03 95% CI: 0.99 ~ 1.07). MR-Egger regression, weighted median, IVW radial method, and weighted mode results are consistent with the results of the IVW method.

Conclusion: This study does not support a genetic link between Parkinson's disease and SARS-CoV-2 infection, and the association observed in previous cohort studies and observational studies may be due to other confounding factors.

Keywords: Mendelian randomization study; Parkinson’s disease; SARS-CoV-2; genetic link; infection.

Figure 1

MR estimates of genetically predicted susceptibility, hospitalization, and severity of COVID-19 on the risk of Parkinson’s disease. The inverse variance weighted method is considered the main method. MR, Mendelian randomization; SNP, Single nucleotide polymorphism; P, p-value; OR, odds ratio; CI, Confidence interval.

Figure 2

MR estimates of genetically predicted risk of Parkinson’s disease on susceptibility, hospitalization, and severity of COVID-19. The inverse variance weighted method is considered the main method. MR, Mendelian randomization; SNP, Single nucleotide polymorphism; P, p-value; OR, odds ratio; CI, Confidence interval.

Figure 3

Results of MR leave-one-out sensitivity analysis. 3-1MR leave−one−out sensitivity analysis for ‘Parkinson’s disease’ on ‘SARS-CoV-2 infection’; 3–2 MR leave−one−out sensitivity analysis for ‘SARS-CoV-2 infection’ on ‘Parkinson’s disease’; 3-3MR leave−one−out sensitivity analysis for ‘Parkinson’s disease’ on ‘Hospitalized COVID-19’; 3-4MR leave−one−out sensitivity analysis for ‘Severe COVID-19’ on ‘Parkinson’s disease’; 3–5 MR leave−one−out sensitivity analysis for ‘Severe COVID-19’ on ‘Parkinson’s disease’; 3–6 MR leave−one−out sensitivity analysis for ‘Parkinson’s disease’ on ‘Severe COVID-19’ MR, Mendelian randomization.