title: Genome-wide association study of HLA-DQB1*06:02 negative essential hypersomnia.
abstract: Essential hypersomnia (EHS), a sleep disorder characterized by excessive daytime sleepiness, can be divided into two broad classes based on the presence or absence of the HLA-DQB1*06:02 allele. HLA-DQB1*06:02-positive EHS and narcolepsy with cataplexy are associated with the same susceptibility genes. In contrast, there are fewer studies of HLA-DQB1*06:02 negative EHS which, we hypothesized, involves a different pathophysiological pathway than does narcolepsy with cataplexy. In order to identify susceptibility genes associated with HLA-DQB1*06:02 negative EHS, we conducted a genome-wide association study (GWAS) of 125 unrelated Japanese EHS patients lacking the HLA-DQB1*06:02 allele and 562 Japanese healthy controls. A comparative study was also performed on 268 HLA-DQB1*06:02 negative Caucasian hypersomnia patients and 1761 HLA-DQB1*06:02 negative Caucasian healthy controls. We identified three SNPs that each represented a unique locus- rs16826005 (P = 1.02E-07; NCKAP5), rs11854769 (P = 6.69E-07; SPRED1), and rs10988217 (P = 3.43E-06; CRAT) that were associated with an increased risk of EHS in this Japanese population. Interestingly, rs10988217 showed a similar tendency in its association with both HLA-DQB1*06:02 negative EHS and narcolepsy with cataplexy in both Japanese and Caucasian populations. This is the first GWAS of HLA-DQB1*06:02 negative EHS, and the identification of these three new susceptibility loci should provide additional insights to the pathophysiological pathway of this condition.
authors: Department of Human Genetics, Graduate School of Medicine, The University of Tokyo , Tokyo , Japan.
authors: Seik-Soon
authors: SS
authors: Khor
authors: Taku
authors: T
authors: Miyagawa
authors: Hiromi
authors: H
authors: Toyoda
authors: Maria
authors: M
authors: Yamasaki
authors: Yoshiya
authors: Y
authors: Kawamura
authors: Hisashi
authors: H
authors: Tanii
authors: Yuji
authors: Y
authors: Okazaki
authors: Tsukasa
authors: T
authors: Sasaki
authors: Ling
authors: L
authors: Lin
authors: Juliette
authors: J
authors: Faraco
authors: Tom
authors: T
authors: Rico
authors: Yutaka
authors: Y
authors: Honda
authors: Makoto
authors: M
authors: Honda
authors: Emmanuel
authors: E
authors: Mignot
authors: Katsushi
authors: K
authors: Tokunaga
keywords: CRAT; EHS; Essential hypersomnia; HLA-DQB1*06:02; NAP5; NCKAP5; Narcolepsy; Narcolepsy with cataplexy; SPRED1
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