Causal effect of systemic lupus erythematosus on psychiatric disorders: A two-sample Mendelian randomization study.

BACKGROUND: This study aims to investigate the association between systemic lupus erythematosus (SLE) and the risk of seven psychiatric disorders through the application of Mendelian randomization (MR) analysis due to previous observational studies that have suggested a potential link between SLE and psychiatric disorders. METHODS: We collected genetic instruments for SLE from a genome-wide association study (GWAS) involving 23,210 individuals. Seven psychiatric traits were enrolled from the recent largest GWAS, including major depression disorder (MDD), generalized anxiety disorder (GAD), schizophrenia (SCZ), bipolar disorder (BID), autism spectrum disorder (ASD), attention deficit/hyperactivity disorder (ADHD), and insomnia. Summary statistics for psychiatric disorders were obtained from different GWAS meta-analysis studies. The inverse variance weighted (IVW) method was used as the main MR analysis. RESULTS: The IVW method indicated that SLE is associated with a higher risk of GAD (OR = 1.072, 95 % CI [1.017-1.129], P = 0.008) and SCZ (OR = 3.242, 95 % CI [1.578-6.660], P = 0.007). However, no evidence was found for the causal associations between SLE and other psychiatric disorders. Further analyses found no evidence of pleiotropy and heterogeneity. CONCLUSIONS: This two-sample MR analysis provides evidence that genetically predicted SLE may increase the risk of GAD and SCZ in a European population. Future studies are needed to elucidate and investigate the mechanisms underlying these causal relationships. Considering the existence of racial genomic heterogeneity, our findings must be viewed with caution.

Susceptibility and severity of COVID-19 and risk of psychiatric disorders in European populations: a Mendelian randomization study.

Background: Observational studies have suggested that COVID-19 increases the prevalence of psychiatric disorders, but the results of such studies are inconsistent. This study aims to investigate the association between COVID-19 and the risk of psychiatric disorders using Mendelian randomization (MR) analysis. Methods: We used summary statistics from COVID-19 Host Genetics Initiative genome-wide association study (GWAS) of COVID-19 involving 2,586,691 participants from European ancestry. Genetic variations of five psychiatric disorders including autism spectrum disorder (ASD) (N = 46,351), bipolar disorder (BID) (N = 51,710), major depressive disorder (MDD) (N = 480,359), anxiety disorder (N = 83,566), and schizophrenia (SCZ) (N = 77,096) were extracted from several GWAS of European ancestry. The inverse-variance weighted (IVW) method as the main MR analysis conducted. We further performed sensitivity analyzes and heterogeneity analyzes as validation of primary MR results. Results: The IVW analysis found that COVID-19 hospitalization phenotype was the risk factor for BID (OR = 1.320, 95% CI = 1.106-1.576, p = 0.002) and SCZ (OR = 1.096, 95% CI = 1.031-1.164, p = 0.002). Moreover, we detected a significant positive genetic correlation between COVID-19 severity and two psychiatric traits, BID (OR = 1.139, 95% CI = 1.033-1.256, p = 0.008) and SCZ (OR = 1.043, 95% CI = 1.005-1.082, p = 0.024). There was no evidence supporting the causal relationship between COVID-19 susceptibility and psychiatric disorders. Conclusion: Our results found that the COVID-19 hospitalization phenotype and COVID-19 severity phenotype might be the potential risks of BID and SCZ in European populations. Therefore, patients infected with SARS-CoV-2 should have enhanced monitoring of their mental status.

Unraveling the link: exploring the causal relationship between diabetes, multiple sclerosis, migraine, and Alzheimer's disease through Mendelian randomization.

Introduction: Observational studies suggested that diabetes mellitus [type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM)], multiple sclerosis (MS), and migraine are associated with Alzheimer's disease (AD). However, the causal link has not been fully elucidated. Thus, we aim to assess the causal link between T1DM, T2DM, MS, and migraine with the risk of AD using a two-sample Mendelian randomization (MR) study. Methods: Genetic instruments were identified for AD, T1DM, T2DM, MS, and migraine respectively from genome-wide association study. MR analysis was conducted mainly using the inverse-variance weighted (IVW) method. Results: The result of IVW method demonstrated that T2DM is causally associated with risk of AD (OR: 1.237, 95% CI: 1.099-1.391, P: 0.0003). According to the IVW method, there is no causal association between TIDM, MS, migraine, and the risk of AD (all p value > 0.05). Here we show, there is a causal link between T2DM and the risk of AD. Conclusion: These findings highlight the significance of active monitoring and prevention of AD in T2DM patients. Further studies are required to actively search for the risk factors of T2DM combined with AD, explore the markers that can predict T2DM combined with AD, and intervene and treat early.