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.