Disturbance of skin sensation and autism spectrum disorder: A bidirectional Mendelian randomization study

Patients with autism spectrum disorder (ASD) commonly experience aberrant skin sensation sensitivity; however, the causal relationship is not yet clear. This study uses a bidirectional Mendelian randomization (MR) method to explore the relationship between disturbance of skin sensation (DSS) and ASD.

Single-nucleotide polymorphisms (SNPs) extracted from the summary data of genome-wide association studies were used as genetic instruments. MR was performed using the inverse-variance-weighted method, with alternate methods (e.g., weighted median, MR-Egger, simple mode, weighted mode, and MR-pleiotropy residual sum and outlier) and multiple sensitivity analyses to assess horizontal pleiotropy and remove outliers.

The results of the analysis using six SNPs as genetic instruments showed that the DSS is associated with an increased risk of ASD (odds ratio = 1.126, 95% confidence interval = 1.029-1.132; p = .010). The results of the sensitivity analyses were robust with no evidence of pleiotropy. The reverse MR analyses showed no causal effects of ASD on DSS.

This study's findings suggest that DSS has potential causal effects on ASD, whereas ASD has no effect on DSS. Thus, skin sensitivity may represent a behavioral marker of ASD, by which some populations could be subtyped in the future.