UTMOST, A Novel Single And Cross-Tissue TWAS (Transcriptome Wide Association Study), Reveals New ASD (Autism Spectrum Disorder) Associated Genes

BackgroundASD is a complex neurodevelopmental disorder which may significantly impact on the affected individuals life. Common variation (SNPs) could explain about 50% of ASD heritability. Despite this fact and the large size of the last GWAS meta-analysis, it is believed that hundreds of risk genes in ASD have yet to be discovered. New tools such as TWAS which integrate tissue-expression and genetic data, are a great approach to identify new ASD susceptibility genes. MethodsThe main goal of this study is to use UTMOST with the public available summary statistics from the largest ASD GWAS meta-analysis as genetic input. In addition, an in silico biological characterization for the novel associated loci was performed. ResultsOur results have demonstrated the association of 4 genes at the brain level (CIPC, PINX1, NKX2-2 and PTPRE) and highlight the association of NKX2-2, MANBA, ERI1 and MITF at the gastrointestinal level. This last finding is quite relevant given the well-established but unexplored relationship between ASD and gastrointestinal symptoms. Cross-tissue analysis has shown the association of NKX2-2 and BLK. ConclusionsUTMOST associated genes together with their in silico biological characterization seems to point to different biological mechanisms underlying ASD etiology not only restricted to brain tissue and involving other body tissues such as the gastrointestinal tissue.