Investigating Genetic Signatures for Sex-Biased miRNA targeted Genes related to Intellectual Disability

Intellectual Disability (ID) often co-occurs with ASD and other diseases, so investigation of Non-syndromic ID (NS-ID) likely provides more accurate insights into genetic causes. As ~80% of NS-ID genes reside on the X-chromosome, contributing to the high male-female ratio in ID patients, we investigated the gender bias in ID by obtaining targeted genes of 13 X-linked and sex-biased miRNAs associated with NS-ID and studying the genetic signatures of 73 brain-expressed (i.e. overexpressed in brain tissues) sex-biased miRNA-targeted genes. Genetic signatures, including Gene Ontology information, disease association, exon numbers, and Protein-Protein Interaction, all of which presented differences between male-biased and female-biased genes, suggest genes' pathogeny by reflecting possible mutations during alternative splicing and pathogenic disruptions of interactions/pathways. Specifically, our result suggests that while the proportion of brainexpressed male-biased genes targeted by X-linked miRNAs is higher, X-linked ID-related genes are more prevalent in females. We also found that sex-biased ID-related genes tend to have more exon numbers, and interactions among miRNA-targeted female-biased genes are significantly higher. Moreover, previously discovered prevalent symptoms in ID patients, such as osteogenesis imperfecta and osteoporosis, are explained by ID-related genes' signatures. Multiple associations between our prioritized genes and ID-related pathways, symptoms, and syndromes further indicate the role miRNA has in targeting plays in the context of ID.