Causality between sleep traits and the risk of frailty: a Mendelian randomization study.

Background: Research based on observation has demonstrated a relationship between sleep traits and frailty; however, it remains uncertain if this correlation indicates causation. The purpose of this study was to look at the causal relationship that exists between frailty and sleep traits. Method: Using summaries from a genome-wide association study of self-reported sleep features and frailty index, we performed a bidirectional Mendelian randomization (MR) analysis. Examining the causal relationships between seven sleep-related traits and frailty was the goal. The major method used to calculate effect estimates was the inverse-variance weighted method, supplemented by the weighted median and MR-Egger approaches. The study investigated pleiotropy and heterogeneity using several methodologies, such as the MR-Egger intercept, the MR-PRESSO approach, and the Cochran's Q test. We took multivariate Mendelian randomization and genetic correlations between related traits to enhance the confidence of the results. Furthermore, we used MRlap to correct for any estimation bias due to sample overlap. Results: Insomnia, napping during the day, and sleep apnea syndrome exhibited a positive connection with the frailty index in forward MR analysis. Conversely, there is a negative link between getting up in the morning, snoring and sleep duration with the frailty index. During the reverse MR analysis, the frailty index exhibited a positive correlation with insomnia, napping during the day, and sleep apnea syndrome, while demonstrating a negative correlation with sleep duration. There was no direct correlation between snoring, chronotype, and frailty. In MVMR analyses, the causal effect of sleep characteristics on frailty indices remained consistent after adjusting for potential confounders including BMI, smoking, and triglycerides. Conclusion: The findings of our investigation yield novel evidence that substantiates the notion of a bidirectional causal connection between sleep traits and frailty. Through the optimization of sleep, it is potentially feasible to hinder, postpone, or even reverse the state of frailty, and we proposed relevant interventions.

Causal association between rheumatoid arthritis and an increased risk of age-related macular degeneration: A Mendelian randomization study.

This study's goal is to evaluate if there is a causal connection between rheumatoid arthritis (RA) and age-related macular degeneration (AMD), despite past epidemiological studies suggesting an association between the 2 disorders. The impact of RA on AMD is still unknown. Mendelian randomization (MR) was utilized in this study to assess the two-sample causal relationship between RA and AMD. Summary data from GWAS for RA and AMD in individuals with all European ancestries were gathered using the IEU GWAS database. The GWAS summary statistics of RA (14,361 RA patients and 43,923 healthy controls) and AMD (14,034 AMD patients and 91,214 controls participated) were obtained from the IEU GWAS database. After identifying suitable instrumental variables in line with the 3 MR assumptions, we conducted MR using the Mendelian randomization-Egger (MR-Egger), weighted median, and inverse variance weighting techniques. The MR-Egger intercept and MR-Polyvalent Residuals and Outliers methods were used to investigate the effects of horizontal pleiotropy. The leave-one-out strategy was used to prevent bias caused by certain single nucleotide polymorphisms. Sensitivity analysis was used to detect the heterogeneity. Using 50 single nucleotide polymorphisms as instrumental variables, this study examined the relationship between RA and AMD and discovered that RA increased the risk of AMD (inverse variance weighting odds ratio [OR] = 1.056, 95% confidence interval [CI] = 1.02-1.09, P = 5.44E-04; weighted median OR = 1.085, 95% CI = 1.04-1.14, P = 4.05E-04; MR-Egger OR = 1.074, 95% CI = 1.01-1.14, P = 2.18E-2). The current investigation demonstrated a causal link between AMD and RA. RA increased the risk of AMD. It is advised that future research concentrate on the processes underlying the relationship between RA and AMD.

Causality between rheumatoid arthritis and the risk of cognitive impairment: a Mendelian randomization study.

BACKGROUND: There is mounting proof that rheumatoid arthritis (RA) and cognitive decline are related. These studies, however, have not all been uniform, and others have not discovered such a correlation. It is essential to investigate the link between RA and cognitive decline. METHOD: We conducted a Mendelian randomization analysis utilizing three different publicly accessible RA GWAS summary datasets and a variety of meticulously verified instrumental variables. We mostly used inverse variance weighting (IVW), as well as MR-Egger, weighted median, MR-PRESSO, and several sensitivity analyses, to figure out the link between RA and cognitive impairment (CI). RESULTS: Our MR study identified the causality between RA and declining cognitive performance (ß = - 0.010, 95% CI of - 0.017 to - 0.003, P = 4.33E-03) and cognitive function (ß = - 0.029, 95% CI of - 0.053 to - 0.005, P = 1.93E-02). The consistent direction of the connection is revealed by sensitivity analysis utilizing the weighted median and the MR-Egger method. Furthermore, we reproduced our findings across two additional RA datasets and found identical outcomes, strengthening the validity of our findings. CONCLUSION: This study offers proof of causality between RA and an increased risk of CI. Our findings highlight the importance of examining RA patients for cognitive ability, which may open up fresh ideas for the prevention of CI.

Rheumatoid arthritis and hypothyroidism: a bidirectional Mendelian randomization study.

Object: Though significant correlations between rheumatoid arthritis (RA) and hypothyroidism have been found in earlier observational studies, their underlying causal relationship is still unknown. Mendelian randomization (MR) was used in the current study to assess the bidirectional causation between RA and hypothyroidism. Method: We gathered summary data from genome-wide association studies (GWASs) of RA and hypothyroidism in people of European descent. Then, using data from the FinnGen consortium, we replicated our findings. Three approaches were employed to assess the causal link between RA and hypothyroidism: MR-Egger, weighted median (WM), and inverse variance weighted (IVW). The pleiotropy and heterogeneity were examined using a variety of techniques, including the MR-Egger intercept, the MR-PRESSO approach, the leave-one-out method, and the Cochran's Q test. Results: The study looked at a bidirectional incidental relationship between RA and hypothyroidism. The risk of hypothyroidism increased with RA (IVW odds ratio (OR) = 1.28, 95% confidence interval (CI) = 1.18-1.39, P = 8.30E-10), as did the risk of secondary hypothyroidism (IVW OR = 1.12, 95% CI = 1.05-1.21, P = 9.64E-4). The results of reverse MR analysis revealed that hypothyroidism (IVW OR = 1.68, 95% CI = 1.51-1.88, P = 4.87E-21) and secondary hypothyroidism (IVW OR = 1.74, 95% CI = 1.50-2.01, P = 1.91E-13) were linked to an increased risk of RA. Additionally, we obtain the same results in the duplicated datasets as well, which makes our results even more reliable. This study revealed no evidence of horizontal pleiotropy. Conclusion: The present study established a bidirectional causal link between RA and hypothyroidism. However, it differs slightly from the findings of prior observational studies, suggesting that future research should concentrate on the interaction mechanisms between RA and hypothyroidism.

Systemic lupus erythematosus and thyroid disease: a Mendelian randomization study.

OBJECTIVES: To clarify the controversy between systemic lupus erythematosus (SLE) and thyroid disease, our study was designed to determine whether or not thyroid problems are associated with SLE. METHODS: We obtained the IEU GWAS database for summary information on genome-wide association studies (GWAS) of SLE and thyroid disease (hypothyroidism and hyperthyroidism) in people with European ancestry. Three approaches were employed to assess the causal link between SLE and thyroid disease: MR-Egger, weighted median (WM), and inverse variance weighted (IVW). The pleiotropy and heterogeneity were examined using a variety of techniques, including the MR-Egger intercept, the MR-PRESSO approach, and the Cochran's Q test. RESULTS: MR analysis revealed a relationship between SLE and an elevated incidence of hypothyroidism (IVW OR: 1.004, 95% CI: [1.003, 1.005], P = 8.45E-16) and hyperthyroidism (IVW OR: 1.0009, 95% CI: [1.0005, 1.0010], P = 1.30E-5). Neither horizontal pleiotropy nor heterogeneity was detected in the sensitivity analysis. CONCLUSION: Our MR study presents strong evidence demonstrating a link between SLE and an elevated risk of thyroid illness. This could help us learn more about what causes SLE and give people with SLE more thorough thyroid function tests and evaluations. Key points • We did not discover modest heterogeneity and pleiotropy in our study. •The findings of this study indicate that SLE is related to an elevated risk of hypothyroidism and hyperthyroidism.