J Rheum Dis.  2022 Jan;29(1):46-51. 10.4078/jrd.2022.29.1.46.

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

• Lee YH
• Song GG

• KMID: 2523459
• DOI: http://doi.org/10.4078/jrd.2022.29.1.46

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.

Keyword

Rheumatoid arthritis; Systemic lupus erythematosus; Autism; Mendelian randomization analysis

Figure

• 

  Figure 1 Forest plot of the causal effects of rheumatoid arthritis- (A) and systemic lupus erythematosus- (B) associated single-nucleotide polymorphisms on the risk for autism spectrum disorder (ASD). IVW: inverse variance weighted, MR: Mendelian randomization.

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  Figure 2 Scatterplots of genetic associations with rheumatoid arthritis (A) and systemic lupus erythematosus (B) versus genetic associations with autism spectrum disorder. The slopes of each line represent causal associations for each method. The blue, green, and dark lines represent the inverse variance-weighted, weighted median, and mendelian randomization‐Egger estimates, respectively. SNP: single-nucleotide polymorphism.

• 

  Figure 3 Funnel plot assessing heterogeneity.

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