The Association Between Functional Variants in Long Non-coding RNAs and the Risk of Autism Spectrum Disorder Was Not Mediated by Gut Microbiota.

The effect of functional variants in long non-coding RNA (lncRNA) gene regions on autism spectrum disorder (ASD) remains unclear. The present study aimed to investigate the association of functional variants located in lncRNA genes with the risk of ASD and explore whether gut microbiota would mediate the relationship. A total of 87 cases and 71 healthy controls were enrolled in the study. MassARRAY platform and 16S rRNA sequencing were respectively applied to assess the genotype of candidate SNPs and gut microbiota of children. The logistic regression models showed that the association between rs2295412 and the risk of ASD was statistically significant after Bonferroni adjustments. The risk of ASD decreased by 19% for each additional C allele carried by children in multiplicative models (OR = 0.81, 95% CI, 0.69-0.94, P = 0.007). Although we identified significant correlations between rs8113922 polymorphisms, Bifidobacteriales, and ASD, the mediating effect of gut microbiota on the relationship of the polymorphisms with the risk of ASD was not significant. The findings demonstrated that functional variants in lncRNA genes play an important role in ASD and gut microbiota could not mediate the association. Future studies are warranted to verify the results and search for more possible mechanisms of variants located in lncRNA genes implicated in ASD.