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

Abstract

BACKGROUND AND AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.