Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
Hum Genet. 2010 Oct;128(4):433-41. doi: 10.1007/s00439-010-0862-z. Epub 2010 Jul 31.
Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness, cataplexy, and a pathological manifestation of rapid eye movement during sleep. Narcoleptic pathogenesis is triggered by both genetic and environmental factors. Recently, development of genome-wide association studies (GWAS) has identified new genetic factors, with many more susceptibility genes yet to be elucidated. Using a new approach that consists of a combination of GWAS and an extensive database search for candidate genes, we picked up 202 candidate genes and performed a replication study in 222 narcoleptic patients and 380 controls. Statistical analysis indicated that six genes, NFATC2, SCP2, CACNA1C, TCRA, POLE, and FAM3D, were associated with narcolepsy (P<0.001). Some of these associations were further supported by gene expression analyses and an association study in essential hypersomnia (EHS), CNS hypersonia similar to narcolepsy. This novel approach will be applicable to other GWAS in the search of disease-related susceptibility genes.
发作性睡病是一种以日间过度嗜睡、猝倒和睡眠中快速眼动期病理性发作为特征的睡眠障碍。发作性睡病的发病机制是由遗传和环境因素共同触发的。最近，全基因组关联研究（GWAS）的发展已经确定了新的遗传因素，但还有更多的易感基因有待阐明。我们采用一种新的方法，将 GWAS 与候选基因的广泛数据库搜索相结合，挑选了 202 个候选基因，并在 222 名发作性睡病患者和 380 名对照者中进行了复制研究。统计分析表明，NFATC2、SCP2、CACNA1C、TCRA、POLE 和 FAM3D 这 6 个基因与发作性睡病相关（P<0.001）。其中一些关联通过基因表达分析和对类似于发作性睡病的中枢性过度睡眠（EHS）的关联研究得到了进一步支持。这种新方法将适用于其他 GWAS 以寻找与疾病相关的易感基因。
