| Literature DB >> 30266950 |
Taku Miyagawa1,2, Seik-Soon Khor3, Hiromi Toyoda3, Takashi Kanbayashi4,5, Aya Imanishi4, Yohei Sagawa4, Nozomu Kotorii6,7, Tatayu Kotorii7, Yu Ariyoshi8, Yuji Hashizume6, Kimihiro Ogi6, Hiroshi Hiejima6, Yuichi Kamei9, Akiko Hida10, Masayuki Miyamoto11, Azusa Ikegami12, Yamato Wada13, Masanori Takami14, Yuichi Higashiyama15, Ryoko Miyake15, Hideaki Kondo16, Yota Fujimura17,18, Yoshiyuki Tamura17, Yukari Taniyama19, Naoto Omata20, Yuji Tanaka20, Shunpei Moriya21, Hirokazu Furuya22,23, Mitsuhiro Kato24,25, Yoshiya Kawamura26, Takeshi Otowa27, Akinori Miyashita28, Hiroto Kojima29, Hiroh Saji29, Mihoko Shimada30,3, Maria Yamasaki3, Takumi Kobayashi3,31, Rumi Misawa3,31, Yosuke Shigematsu32, Ryozo Kuwano28, Tsukasa Sasaki33, Jun Ishigooka34, Yuji Wada20, Kazuhito Tsuruta19, Shigeru Chiba17, Fumiaki Tanaka15, Naoto Yamada14, Masako Okawa35,36,37, Kenji Kuroda13, Kazuhiko Kume12,38,39, Koichi Hirata11, Naohisa Uchimura6, Tetsuo Shimizu4,5, Yuichi Inoue37,40, Yutaka Honda41, Kazuo Mishima4,5,10, Makoto Honda30,41, Katsushi Tokunaga3.
Abstract
Essential hypersomnia (EHS) is a lifelong disorder characterized by excessive daytime sleepiness without cataplexy. EHS is associated with human leukocyte antigen (HLA)-DQB1*06:02, similar to narcolepsy with cataplexy (narcolepsy). Previous studies suggest that DQB1*06:02-positive and -negative EHS are different in terms of their clinical features and follow different pathological pathways. DQB1*06:02-positive EHS and narcolepsy share the same susceptibility genes. In the present study, we report a genome-wide association study with replication for DQB1*06:02-negative EHS (408 patients and 2247 healthy controls, all Japanese). One single-nucleotide polymorphism, rs10988217, which is located 15-kb upstream of carnitine O-acetyltransferase (CRAT), was significantly associated with DQB1*06:02-negative EHS (P = 7.5 × 10-9, odds ratio = 2.63). The risk allele of the disease-associated SNP was correlated with higher expression levels of CRAT in various tissues and cell types, including brain tissue. In addition, the risk allele was associated with levels of succinylcarnitine (P = 1.4 × 10-18) in human blood. The leading SNP in this region was the same in associations with both DQB1*06:02-negative EHS and succinylcarnitine levels. The results suggest that DQB1*06:02-negative EHS may be associated with an underlying dysfunction in energy metabolic pathways.Entities:
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Year: 2018 PMID： 30266950 DOI： 10.1038/s10038-018-0518-8
Source DB: PubMed Journal: J Hum Genet ISSN： 1434-5161 Impact factor: 3.172