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Some viruses, such as varicella zoster virus, are associated with severe dementia. The present study aims to identify the causal link between chickenpox and dementia. To date, the largest publicly available genome‐wide association study (GWAS) for chickenpox (710 cases and 211 856 controls from European individuals) and for dementia (5933 cases and 212 859 controls from European individuals) were used to performed this two‐sample Mendelian randomization (MR) study. We found no significant pleiotropy or heterogeneity in all seven selected chickenpox genetic instrumental variants in dementia GWAS. Of seven chickenpox genetic variants, two are located in the intergenic region and five are located in intron. We found that as chickenpox genetically increased, dementia risk increased based on an inverse‐variance weighted analysis (β = 0.070, 95% confidence interval [CI] for β: 0.014–0.126; odds ratio [OR] = 1.073, 95% CI for OR: 1.015–1.134; p = 0.014) and weighted median (β = 0.071, 95% CI for β: 0.002–0.141; OR = 1.074, 95% CI for OR: 1.002–1.152; p = 0.045). Reverse MR analysis showed no causal effect of dementia on chickenpox. Our analysis suggests a causal effect of genetically increased chickenpox on dementia risk. Thus, chickenpox may be a potential risk factor for dementia. [ABSTRACT FROM AUTHOR]

Observational studies have suggested a suspected association between varicella‐zoster virus (VZV) infection and multiple sclerosis (MS), but the connection has remained unclear. The aim of the present study is to evaluate the causal relationship between chickenpox which is caused by VZV infection and MS. We performed a two‑sample Mendelian randomization analysis to investigate the association of chickenpox with MS using summary statistics from genome‑wide association studies (GWAS). The GWAS summary statistics data for chickenpox was from the 23andMe cohort including 107 769 cases and 15 982 controls. A large summary of statistical data from the International Multiple Sclerosis Genetics Consortium (IMSGC) was used as the outcome GWAS data set, including 14 802 MS cases and 26 703 controls. We found evidence of a significant association between genetically predicted chickenpox and risk of MS (odds ratio [OR] = 35.27, 95% confidence interval [CI] = 22.97–54.17, p = 1.46E−59). Our findings provided evidence indicating a causal effect of chickenpox on MS. Further elucidations of this association and underlying mechanisms are needed for identifying feasible interventions to promote MS prevention. [ABSTRACT FROM AUTHOR]

Background: Glutamine family amino acids such as glutamate, pyroglutamate, and glutamine have been shown to play important roles in COVID-19. However, it is still unclear about the role of pyroglutamate in COVID-19. Thus, we use a two-sample Mendelian randomization (MR) study to identify the genetic causal link between blood pyroglutamine levels and COVID-19 risk. Methods: Pyroglutamine genetic instrumental variables (IVs) were chosen from the largest pyroglutamine-associated genome-wide association studies (GWAS). The largest COVID-19 GWAS dataset was employed to evaluate the causal link between blood pyroglutamine levels and COVID-19 risk using two-sample MR analysis. Results: We found no significant pleiotropy or heterogeneity of pyroglutamine-associated genetic IVs in COVID-19 GWAS. Interestingly, we found that as pyroglutamine genetically increased, the risk of COVID-19 decreased using inverse variance weighted (IVW) (Beta = − 0.644, p = 0.003; OR = 0.525, 95% CI [0.346–0.798]) and weighted median (Beta = − 0.609, p = 0.013; OR = 0.544, 95% CI [0.337–0.878]). Conclusion: Our analysis suggests a causal link between genetically increased pyroglutamine and reduced risk of COVID-19. Thus, pyroglutamine may be a protective factor for patients with COVID-19. [ABSTRACT FROM AUTHOR]

Although individuals with coronavirus disease 2019 (COVID‐19) are known to be at increased risk for other conditions resulting from pathogenic changes (including metaplastic or anaplastic) in the lungs and other organs and organ systems, it is still unknown whether COVID‐19 affects childhood intelligence. The present two‐sample Mendelian randomization study aims to identify the genetic causal link between COVID‐19 and childhood intelligence. Four COVID‐19 genetic instrumental variants (IVs) were chosen from the largest genome‐wide association studies (GWAS) for COVID‐19 (hospitalized vs. population) (6406 cases and 902 088 controls of European ancestry). The largest childhood intelligence GWAS (n = 12 441 individuals of European ancestry) was used to evaluate the effect of the identified COVID‐19‐associated genetic IVs on childhood intelligence. We found that as the genetic susceptibility to COVID‐19 increased, childhood intelligence followed a decreasing trend, according to mr_egger (β = −0.156; p = 0.601; odds ratio [OR] = 0.856; 95% confidence interval [CI]: 0.522–1.405), simple mode (β = −0.126; p = 0.240; OR = 0.882; 95% CI: 0.745–1.044), and weighted mode (β = −0.121; p = 0.226; OR = 0.886; 95% CI: 0.758–1.036) analyses. This trend was further demonstrated by the weighted median (β = −0.134; p = 0.031; OR = 0.875; 95% CI: 0.774–0.988) and the inverse variance weighted (β = −0.152; p = 0.004; OR = 0.859; 95% CI: 0.776–0.952). Our analysis suggests a causal link between genetically increased COVID‐19 and decreased childhood intelligence. Thus, COVID‐19 may be a risk factor for declines in childhood intelligence. [ABSTRACT FROM AUTHOR]

Objectives: To resolve the ongoing debate on the role of plasma omega-3 fatty acids in rheumatoid arthritis (RA), we attempted to identify the association between omega-3 intake and the risk of RA. Methods: We analyzed data from the largest genome-wide association study (GWAS) for omega-3 fatty acids (N = 114,999 of European ancestry) and RA (14,361 cases and 43,923 controls of European ancestry). Mendelian randomization-egger_intercept, MR-PRESSO, and Cochran's Q test were used to determine pleiotropy and heterogeneity. Egger, weighted median, inverse variance weighted (IVW), simple mode, and weighted mode were used to evaluate the causal association of plasma omega-3 levels on RA. Results: We found no significant pleiotropy, heterogeneity, and bias among the omega-3 genetic instrumental variables (IVs) in RA GWAS datasets. MR analysis demonstrated that as omega-3 levels genetically increased, the risk of MS increased using MR-egger (Beta = 0.137, p = 0.037; OR = 1.146, 95% CI: [1.014, 1.296]), weighted median (Beta = 0.162, p = 0.001; OR = 1.176, 95% CI: [1.070, 1.292]), IVW (Beta = 0.102, p = 0.025; OR = 1.108, 95% CI: [1.013, 1.211]), simple mode (Beta = 0.219, p = 0.149; OR = 1.245, 95% CI: [0.931, 1.665]), and weighted mode (Beta = 0.146, p = 0.006; OR = 1.157, 95% CI: [1.051, 1.274]). Conclusions: Our analysis suggested a causal association between genetically increased plasma omega-3 levels and the increased risk of RA in populations with European ancestry. Thus, to reduce the risk of RA, those of European descent should reduce omega-3 intake. Key Points • No significant pleiotropy or heterogeneity among the omega-3 genetic IVs in RA GWAS datasets. • Genetically increased plasma omega-3 levels enhanced the risk of RA in European lineages. [ABSTRACT FROM AUTHOR]