• Jun Mitsui.
• Department of Neurology, The University of Tokyo.
• Rinsho Shinkeigaku. 2013 Jan 1; 53 (11): 1336-8.

AbstractOver the past decade, genome-wide association studies (GWASs) using common polymorphisms have been conducted to identify genetic risks associated with sporadic diseases. Although GWASs have successfully revealed numerous susceptibility genes for neurodegenerative diseases, the odds ratios associated with these risk alleles are generally low and account for only a small proportion of estimated familial clustering. Emerging new technologies for nucleotide sequencing such as exome sequencing has provided an exhaustive list of variants, which will eventually enable us to explore the role of low-frequency variants of large effect sizes in sporadic neurodegenerative diseases. However, it is still a statistical challenge to determine which variants are relevant to diseases among the numerous candidates, and large sample sizes will be required. Using the clues provided by rare familial cases, we have recently identified strong genetic factors in Parkinson diseases and in multiple system atrophy based on the candidate gene approach. Focusing on the familial aggregation may be an efficient approach to identifying risk alleles of large effect sizes in apparently sporadic neurodegenerative diseases.

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