Relevance to Autism

An intronic SNP in the MAPT gene (rs141455452) was found to be significantly associated with ASD (P-value 9.0E-07) in a genome-wide association meta-analysis of 18,381 ASD cases and 27,969 controls from iPSYCH and the Psychiatric Genomic Consortium (PGC) in Grove et al., 2019. A transcriptome-wide association study (TWAS) of 7,805 ASD proband-parent trios, which was subsequently replicated using 35,740 independent samples, using eQTL and splicing quantitative trait loci in 12 brain tissues from GTEx and the CommonMind Consortium (CMC) in Huang et al., 2021 identified MAPT as a gene whose transcriptome-wide association with ASD remained significant after a stringent Bonferroni correction for all genes and all tissues in the analysis (meta-analysis P-value 5.67E-09 in CMC DLPFC-splicing tissue).

Molecular Function

This gene encodes the microtubule-associated protein tau (MAPT) whose transcript undergoes complex, regulated alternative splicing, giving rise to several mRNA species. MAPT transcripts are differentially expressed in the nervous system, depending on stage of neuronal maturation and neuron type. MAPT gene mutations have been associated with several neurodegenerative disorders such as Alzheimer's disease, Pick's disease, frontotemporal dementia, cortico-basal degeneration and progressive supranuclear palsy.

External Links

References