Mendelian Randomization Research on the Relationship Between Rheumatoid Arthritis and Systemic Lupus Erythematosus and the Risk of Autistic Spectrum Disorder

ABSTRACT

Objective@#The purpose of this study was to examine whether there is a causal link between rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) and autism spectrum disorder (ASD). @*Methods@#We used inverse variance weighted (IVW), weighted median, and MR-Egger regression methods to perform two-sample Mendelian randomization (MR) study using publicly available summary statistics datasets. In addition, we employed genome-wide association studies (GWASs) for RA and SLE as exposure and an ASD GWAS as an outcome. @*Results@#Thirty-three and 28 single-nucleotide polymorphisms from RA and SLE GWASs were selected as instrumental variables for ASD. The IVW method revealed no evidence supporting a causal association between RA and SLE and risk for ASD (beta=−0.077, standard error [SE]=0.041, p=0.062; beta=0.014, SE=0.021, p=0.493). The weighted median approach yielded no evidence of any causal association between RA and SLE and risk for ASD (beta=−0.071, SE=0.058, p=0.223; beta=0.045, SE=0.030, p=0.130). MR-Egger analysis demonstrated no causal association between RA and SLE and risk for ASD (beta=−0.062, SE=0.079, p=0.434; beta=0.048, SE=0.043, p=0.273). The MR results calculated using IVW, the median weighted and the MR-Egger regression approaches were consistent. @*Conclusion@#The findings of the MR analysis did not support a causal relationship between RA or SLE and the risk of ASD.