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.