Elucidation of molecular basis of brain diseases based on personal genome analysis

Project leader:Shoji Tsuji,The University of Tokyo

This project will elucidate molecular basis of brain diseases based on personal genome analysis. Genome-wide association studies (GWAS) based on the “common disease-common variants hypothesis” are currently undertaken to elucidate disease-relevant alleles. Although GWAS have successfully revealed numerous susceptibility genes for neurodegenerative diseases,odds ratios associated with risk alleles are generally low and account for only a small proportion of estimated heritability. Recent studies have revealed that the effect sizes of the disease-relevant alleles that are identified based on comprehensive resequencing of large data are substantially larger than those identified by GWAS. These findings strongly argue for the role of the “common disease-multiple rare variants hypothesis” in sporadic neurodegenerative diseases. Given the rapidly improving technologies of next generation sequencing NGS),we expect that NGS will eventually enable us to identify all the variants in an individual’s personal genome,in particular,clinically relevant alleles.