The relationship of immune cells with autism spectrum disorder: a bidirectional Mendelian randomization study

Observational studies have indicated a correlation between immunological inflammation and the risk of autism spectrum disorder (ASD). However, the causal relationship between immunological inflammation and ASD remains uncertain.

Immunity-wide data sources were retrieved from the GWAS catalog. Genetic summary data on ASD were retrieved from two independent GWAS. We performed two independent bi-directional, two-sample Mendelian randomization (MR) analyses and a meta-analysis based on the two independent MR estimates to assess the causal relationship between ASD and immune cell signatures.

We have discovered 26 potential correlations between genetic predisposition in the immunophenotypes and ASD. The meta-analysis of the two inverse variance weighted (IVW)-produced estimates provided further evidence supporting the potential causal relationship between immunophenotypes and ASD. Based on the findings of the reverse MR analysis, it was determined that there are two potential negative causal relationships between ASD and immunophenotypes. However, the meta-analysis of the two IVW-derived MR estimates indicated that immunophenotypes were not significantly influenced by ASD (OR = 0.87, 95% CI = 0.73 -1.03, P = 0.09; OR = 0.91, 95% CI = 0.81-1.01, P = 0.08).

This study expanded immune cell subtypes that were potentially causally associated with ASD risk as well as identified ASD-specific immune cell subtypes. The discovery has the potential to lead to earlier detection and more effective treatment techniques.