An association analysis of HLA-DQB1 with narcolepsy without cataplexy and idiopathic hypersomnia with/without long sleep time in a Japanese population

Taku Miyagawa; Hiromi Toyoda; Takashi Kanbayashi; Aya Imanishi; Yohei Sagawa; Nozomu Kotorii; Tatayu Kotorii; Yuji Hashizume; Kimihiro Ogi; Hiroshi Hiejima; Yuichi Kamei; Akiko Hida; Masayuki Miyamoto; Azusa Ikegami; Yamato Wada; Masanori Takami; Yota Fujimura; Yoshiyuki Tamura; Naoto Omata; Yasuhiro Masuya; Hideaki Kondo; Shunpei Moriya; Hirokazu Furuya; Mitsuhiro Kato; Hiroto Kojima; Koichi Kashiwase; Hiroh Saji; Seik-Soon Khor; Maria Yamasaki; Jun Ishigooka; Yuji Wada; Shigeru Chiba; Naoto Yamada; Masako Okawa; Kenji Kuroda; Kazuhiko Kume; Koichi Hirata; Naohisa Uchimura; Tetsuo Shimizu; Yuichi Inoue; Yutaka Honda; Kazuo Mishima; Makoto Honda; Katsushi Tokunaga

doi:10.1038/hgv.2015.31

An association analysis of HLA-DQB1 with narcolepsy without cataplexy and idiopathic hypersomnia with/without long sleep time in a Japanese population

Hum Genome Var. 2015 Sep 17:2:15031. doi: 10.1038/hgv.2015.31. eCollection 2015.

Authors

Taku Miyagawa¹, Hiromi Toyoda¹, Takashi Kanbayashi², Aya Imanishi³, Yohei Sagawa³, Nozomu Kotorii⁴, Tatayu Kotorii⁵, Yuji Hashizume⁶, Kimihiro Ogi⁶, Hiroshi Hiejima⁶, Yuichi Kamei⁷, Akiko Hida⁸, Masayuki Miyamoto⁹, Azusa Ikegami¹⁰, Yamato Wada¹¹, Masanori Takami¹², Yota Fujimura¹³, Yoshiyuki Tamura¹⁴, Naoto Omata¹⁵, Yasuhiro Masuya¹⁵, Hideaki Kondo¹⁶, Shunpei Moriya¹⁷, Hirokazu Furuya¹⁸, Mitsuhiro Kato¹⁹, Hiroto Kojima²⁰, Koichi Kashiwase²¹, Hiroh Saji²⁰, Seik-Soon Khor¹, Maria Yamasaki¹, Jun Ishigooka¹⁷, Yuji Wada¹⁵, Shigeru Chiba¹⁴, Naoto Yamada¹², Masako Okawa²², Kenji Kuroda¹¹, Kazuhiko Kume²³, Koichi Hirata⁹, Naohisa Uchimura⁶, Tetsuo Shimizu², Yuichi Inoue²⁴, Yutaka Honda²⁵, Kazuo Mishima⁸, Makoto Honda²⁶, Katsushi Tokunaga¹

Affiliations

¹ Department of Human Genetics, Graduate School of Medicine, The University of Tokyo , Tokyo, Japan.
² Department of Neuropsychiatry, Akita University School of Medicine, Akita, Japan; International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Ibaraki, Japan.
³ Department of Neuropsychiatry, Akita University School of Medicine , Akita, Japan.
⁴ Department of Neuropsychiatry, Kurume University School of Medicine, Fukuoka, Japan; Kotorii Isahaya Hospital, Nagasaki, Japan.
⁵ Kotorii Isahaya Hospital , Nagasaki, Japan.
⁶ Department of Neuropsychiatry, Kurume University School of Medicine , Fukuoka, Japan.
⁷ Sleep Disorder Center, National Center Hospital, National Center of Neurology and Psychiatry , Tokyo, Japan.
⁸ Department of Psychophysiology, National Institute of Mental Health, National Center of Neurology and Psychiatry , Tokyo, Japan.
⁹ Department of Neurology, Dokkyo Medical University , Tochigi, Japan.
¹⁰ Sleep Center, Kuwamizu Hospital , Kumamoto, Japan.
¹¹ Department of Psychiatry, Hannan Hospital , Osaka, Japan.
¹² Department of Psychiatry, Shiga University of Medical Science , Shiga, Japan.
¹³ Department of Psychiatry and Neurology, Asahikawa Medical University, Hokkaido, Japan; Department of General Medicine, Faculty of Medicine, Shimane University, Shimane, Japan.
¹⁴ Department of Psychiatry and Neurology, Asahikawa Medical University , Hokkaido, Japan.
¹⁵ Department of Neuropsychiatry, Faculty of Medical Sciences, University of Fukui , Fukui, Japan.
¹⁶ Center for Sleep Medicine, Saiseikai Nagasaki Hospital , Nagasaki, Japan.
¹⁷ Department of Psychiatry, Tokyo Women's Medical University School of Medicine , Tokyo, Japan.
¹⁸ Department of Neurology, Neuro-Muscular Center, National Omuta Hospital, Fukuoka, Japan; Department of Neurology, Kochi Medical School, Kochi University, Kochi, Japan.
¹⁹ Department of Pediatrics, Yamagata University Faculty of Medicine, Yamagata, Japan; Department of Pediatrics, Showa University School of Medicine, Tokyo, Japan.
²⁰ HLA Foundation Laboratory , Kyoto, Japan.
²¹ Department of HLA Laboratory, Japanese Red Cross Kanto-Koshinetsu Block Blood Center , Tokyo, Japan.
²² Department of Sleep Medicine, Shiga University of Medical Science, Shiga, Japan; Japan Foundation for Neuroscience and Mental Health, Tokyo, Japan; Department of Somnology, Tokyo Medical University, Tokyo, Japan.
²³ Sleep Center, Kuwamizu Hospital, Kumamoto, Japan; Department of Stem Cell Biology, Institute of Molecular Genetics and Embryology, Kumamoto University, Kumamoto, Japan; Department of Neuropharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Aichi, Japan.
²⁴ Department of Somnology, Tokyo Medical University, Tokyo, Japan; Japan Somnology Center, Neuropsychiatric Research Institute, Tokyo, Japan.
²⁵ Japan Somnology Center, Neuropsychiatric Research Institute , Tokyo, Japan.
²⁶ Japan Somnology Center, Neuropsychiatric Research Institute, Tokyo, Japan; Sleep Disorders Project, Department of Psychiatry and Behavioral Sciences, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.

Abstract

Narcolepsy without cataplexy (NA w/o CA) (narcolepsy type 2) is a lifelong disorder characterized by excessive daytime sleepiness and rapid eye movement (REM) sleep abnormalities, but no cataplexy. In the present study, we examined the human leukocyte antigen HLA-DQB1 in 160 Japanese patients with NA w/o CA and 1,418 control subjects. Frequencies of DQB1*06:02 were significantly higher in patients with NA w/o CA compared with controls (allele frequency: 16.6 vs. 7.8%, P=1.1×10(-7), odds ratio (OR)=2.36; carrier frequency: 31.3 vs. 14.7%, P=7.6×10(-8), OR=2.64). Distributions of HLA-DQB1 alleles other than DQB1*06:02 were compared between NA w/o CA and narcolepsy with cataplexy (NA-CA) to assess whether the genetic backgrounds of the two diseases have similarities. The distribution of the HLA-DQB1 alleles in DQB1*06:02-negative NA w/o CA was significantly different from that in NA-CA (P=5.8×10(-7)). On the other hand, the patterns of the HLA-DQB1 alleles were similar between DQB1*06:02-positive NA w/o CA and NA-CA. HLA-DQB1 analysis was also performed in 186 Japanese patients with idiopathic hypersomnia (IHS) with/without long sleep time, but no significant associations were observed.