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COVID-19 and risk of neurodegenerative disorders: A Mendelian randomization study.

ABSTRACT: Emerging evidence has suggested a close correlation between COVID-19 and neurodegenerative disorders. However, whether there exists a causal association and the effect direction remains unknown. To examine the causative role of COVID-19 in the risk of neurodegenerative disorders, we estimated their genetic correlation, and then conducted a two-sample Mendelian randomization analysis using summary statistics from genome-wide association studies of susceptibility, hospitalization, and severity of COVID-19, as well as six major neurodegenerative disorders including Alzheimer's disease (AD), amyotrophic lateral sclerosis, frontotemporal dementia, Lewy body dementia, multiple sclerosis, and Parkinson's disease. We identified a significant and positive genetic correlation between hospitalization of COVID-19 and AD (genetic correlation: 0.23, P = 8.36E-07). Meanwhile, hospitalization of COVID-19 was significantly associated with a higher risk of AD (OR: 1.02, 95% CI: 1.01-1.03, P: 1.19E-03). Consistently, susceptibility (OR: 1.05, 95% CI: 1.01-1.09, P: 9.30E-03) and severity (OR: 1.01, 95% CI: 1.00-1.02, P: 0.012) of COVID-19 were nominally associated with higher risk of AD. The results were robust under all sensitivity analyses. These results demonstrated that COVID-19 could increase the risk of AD. Future development of preventive or therapeutic interventions could attach importance to this to alleviate the complications of COVID-19.

SUBMITTER: Li C

PROVIDER: S-EPMC9281279 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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COVID-19 and risk of neurodegenerative disorders: A Mendelian randomization study.

Li Chunyu C Liu Jiayan J Lin Junyu J Shang Huifang H

Translational psychiatry 20220714 1

Emerging evidence has suggested a close correlation between COVID-19 and neurodegenerative disorders. However, whether there exists a causal association and the effect direction remains unknown. To examine the causative role of COVID-19 in the risk of neurodegenerative disorders, we estimated their genetic correlation, and then conducted a two-sample Mendelian randomization analysis using summary statistics from genome-wide association studies of susceptibility, hospitalization, and severity of ...[more]

PMID: 35835752

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Project description:BackgroundObservational studies have linked exposure to fine (PM2.5) and coarse (PM10) particulate matter air pollution with adverse COVID-19 outcomes, including higher incidence and mortality. However, some studies questioned the effect of air pollution on COVID-19 susceptibility, raising questions about the causal nature of these associations. To address this, a less biased method like Mendelian randomization (MR) is utilized, which employs genetic variants as instrumental variables to infer causal relationships in observational data.MethodWe performed two-sample MR analysis using public genome-wide association studies data. Instrumental variables correlated with PM2.5 concentration, PM2.5 absorbance, PM2.5-10 concentration and PM10 concentration were identified. The inverse variance weighted (IVW), robust adjusted profile score (RAPS) and generalized summary data-based Mendelian randomization (GSMR) methods were used for analysis.ResultsIVW MR analysis showed PM2.5 concentration [odd ratio (OR) = 3.29, 95% confidence interval (CI) 1.48-7.35, P-value = 0.0036], PM2.5 absorbance (OR = 5.62, 95%CI 1.98-15.94, P-value = 0.0012), and PM10 concentration (OR = 3.74, 95%CI 1.52-9.20, P-value = 0.0041) increased the risk of COVID-19 severity after Bonferroni correction. Further validation confirmed PM2.5 absorbance was associated with heightened COVID-19 severity (OR = 6.05, 95%CI 1.99-18.38, P-value = 0.0015 for RAPS method; OR = 4.91, 95%CI 1.65-14.59, P-value = 0.0042 for GSMR method) and hospitalization (OR = 3.15, 95%CI 1.54-6.47, P-value = 0.0018 for RAPS method). No causal links were observed between particulate matter exposure and COVID-19 susceptibility.ConclusionsOur study established a causal relationship between smaller particle pollution, specifically PM2.5, and increased risk of COVID-19 severity and hospitalization. These findings highlight the importance of improving air quality to mitigate respiratory disease progression.

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COVID-19 and risk of neurodegenerative disorders: A Mendelian randomization study.

Publications

COVID-19 and risk of neurodegenerative disorders: A Mendelian randomization study.

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