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To identify susceptibility genes that account for the heritability seen for complex traits, genome-wide association studies (GWAS) employing common single nucleotide polymorphisms (SNPs) have been conducted. The theoretical framework for GWAS is the 'common disease-common variant hypothesis'. Although GWAS have successfully revealed numerous susceptibility genes for common diseases, they generally account for only a small proportion of estimated heritability. In contrast, the prominent role of rare variants in neurodegenerative disease is best highlighted by the recent discovery of the glucocerebrosidase gene (GBA) as a robust genetic risk factor for Parkinson disease. Emerging new technology of next-generation sequencer will be a promising tool which enables an efficient search for remaining disease-relevant alleles.

Genetics of sporadic disease: insights from high-throughput sequencing -Parkinson disease-