PMID- 30266950
OWN - NLM
STAT- MEDLINE
DCOM- 20181221
LR  - 20181221
IS  - 1435-232X (Electronic)
IS  - 1434-5161 (Linking)
VI  - 63
IP  - 12
DP  - 2018 Dec
TI  - A variant at 9q34.11 is associated with HLA-DQB1*06:02 negative essential 
      hypersomnia.
PG  - 1259-1267
LID - 10.1038/s10038-018-0518-8 [doi]
AB  - 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 x 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 x 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.
FAU - Miyagawa, Taku
AU  - Miyagawa T
AD  - Sleep Disorders Project, Department of Psychiatry and Behavioral Sciences, Tokyo 
      Metropolitan Institute of Medical Science, Tokyo, Japan. 
      miyagawa-taku@umin.ac.jp.
AD  - Department of Human Genetics, Graduate School of Medicine, The University of 
      Tokyo, Tokyo, Japan. miyagawa-taku@umin.ac.jp.
FAU - Khor, Seik-Soon
AU  - Khor SS
AUID- ORCID: 0000-0002-6809-4731
AD  - Department of Human Genetics, Graduate School of Medicine, The University of 
      Tokyo, Tokyo, Japan.
FAU - Toyoda, Hiromi
AU  - Toyoda H
AD  - Department of Human Genetics, Graduate School of Medicine, The University of 
      Tokyo, Tokyo, Japan.
FAU - Kanbayashi, Takashi
AU  - Kanbayashi T
AD  - Department of Neuropsychiatry, Akita University School of Medicine, Akita, Japan.
AD  - International Institute for Integrative Sleep Medicine (WPI-IIIS), University of 
      Tsukuba, Ibaraki, Japan.
FAU - Imanishi, Aya
AU  - Imanishi A
AD  - Department of Neuropsychiatry, Akita University School of Medicine, Akita, Japan.
FAU - Sagawa, Yohei
AU  - Sagawa Y
AD  - Department of Neuropsychiatry, Akita University School of Medicine, Akita, Japan.
FAU - Kotorii, Nozomu
AU  - Kotorii N
AD  - Department of Neuropsychiatry, Kurume University School of Medicine, Fukuoka, 
      Japan.
AD  - Kotorii Isahaya Hospital, Nagasaki, Japan.
FAU - Kotorii, Tatayu
AU  - Kotorii T
AD  - Kotorii Isahaya Hospital, Nagasaki, Japan.
FAU - Ariyoshi, Yu
AU  - Ariyoshi Y
AD  - Ariyoshi Sleep Clinic, Fukuoka, Japan.
FAU - Hashizume, Yuji
AU  - Hashizume Y
AD  - Department of Neuropsychiatry, Kurume University School of Medicine, Fukuoka, 
      Japan.
FAU - Ogi, Kimihiro
AU  - Ogi K
AD  - Department of Neuropsychiatry, Kurume University School of Medicine, Fukuoka, 
      Japan.
FAU - Hiejima, Hiroshi
AU  - Hiejima H
AD  - Department of Neuropsychiatry, Kurume University School of Medicine, Fukuoka, 
      Japan.
FAU - Kamei, Yuichi
AU  - Kamei Y
AD  - Department of Laboratory Medicine, National Center Hospital, National Center of 
      Neurology and Psychiatry, Tokyo, Japan.
FAU - Hida, Akiko
AU  - Hida A
AD  - Department of Sleep-Wake Disorders, National Institute of Mental Health, National 
      Center of Neurology and Psychiatry, Tokyo, Japan.
FAU - Miyamoto, Masayuki
AU  - Miyamoto M
AD  - Department of Neurology, Dokkyo Medical University, Tochigi, Japan.
FAU - Ikegami, Azusa
AU  - Ikegami A
AD  - Sleep Center, Kuwamizu Hospital, Kumamoto, Japan.
FAU - Wada, Yamato
AU  - Wada Y
AD  - Department of Psychiatry, Hannan Hospital, Osaka, Japan.
FAU - Takami, Masanori
AU  - Takami M
AD  - Department of Psychiatry, Shiga University of Medical Science, Shiga, Japan.
FAU - Higashiyama, Yuichi
AU  - Higashiyama Y
AD  - Department of Neurology and Stroke Medicine, Yokohama City University Graduate 
      School of Medicine, Kanagawa, Japan.
FAU - Miyake, Ryoko
AU  - Miyake R
AD  - Department of Neurology and Stroke Medicine, Yokohama City University Graduate 
      School of Medicine, Kanagawa, Japan.
FAU - Kondo, Hideaki
AU  - Kondo H
AD  - Center for Sleep Medicine, Saiseikai Nagasaki Hospital, Nagasaki, Japan.
FAU - Fujimura, Yota
AU  - Fujimura Y
AD  - Department of Psychiatry and Neurology, Asahikawa Medical University, Hokkaido, 
      Japan.
AD  - Department of Psychiatry, Tokyo Medical University Hachioji Medical Center, 
      Tokyo, Japan.
FAU - Tamura, Yoshiyuki
AU  - Tamura Y
AD  - Department of Psychiatry and Neurology, Asahikawa Medical University, Hokkaido, 
      Japan.
FAU - Taniyama, Yukari
AU  - Taniyama Y
AD  - Department of Neurology, Junwakai Memorial Hospital, Miyazaki, Japan.
FAU - Omata, Naoto
AU  - Omata N
AD  - Department of Neuropsychiatry, Faculty of Medical Sciences, University of Fukui, 
      Fukui, Japan.
FAU - Tanaka, Yuji
AU  - Tanaka Y
AD  - Department of Neuropsychiatry, Faculty of Medical Sciences, University of Fukui, 
      Fukui, Japan.
FAU - Moriya, Shunpei
AU  - Moriya S
AD  - Department of Psychiatry, Tokyo Women's Medical University School of Medicine, 
      Tokyo, Japan.
FAU - Furuya, Hirokazu
AU  - Furuya H
AD  - Department of Neurology, Neuro-Muscular Center, National Omuta Hospital, Fukuoka, 
      Japan.
AD  - Department of Neurology, Kochi Medical School, Kochi University, Kochi, Japan.
FAU - Kato, Mitsuhiro
AU  - Kato M
AD  - Department of Pediatrics, Yamagata University Faculty of Medicine, Yamagata, 
      Japan.
AD  - Department of Pediatrics, Showa University School of Medicine, Tokyo, Japan.
FAU - Kawamura, Yoshiya
AU  - Kawamura Y
AD  - Department of Psychiatry, Shonan Kamakura General Hospital, Kanagawa, Japan.
FAU - Otowa, Takeshi
AU  - Otowa T
AD  - Graduate School of Clinical Psychology, Teikyo Heisei University Major of 
      Professional Clinical Psychology, Tokyo, Japan.
FAU - Miyashita, Akinori
AU  - Miyashita A
AD  - Department of Molecular Genetics, Center for Bioresources, Brain Research 
      Institute, Niigata University, Niigata, Japan.
FAU - Kojima, Hiroto
AU  - Kojima H
AD  - HLA Foundation Laboratory, Kyoto, Japan.
FAU - Saji, Hiroh
AU  - Saji H
AD  - HLA Foundation Laboratory, Kyoto, Japan.
FAU - Shimada, Mihoko
AU  - Shimada M
AD  - Sleep Disorders Project, Department of Psychiatry and Behavioral Sciences, Tokyo 
      Metropolitan Institute of Medical Science, Tokyo, Japan.
AD  - Department of Human Genetics, Graduate School of Medicine, The University of 
      Tokyo, Tokyo, Japan.
FAU - Yamasaki, Maria
AU  - Yamasaki M
AD  - Department of Human Genetics, Graduate School of Medicine, The University of 
      Tokyo, Tokyo, Japan.
FAU - Kobayashi, Takumi
AU  - Kobayashi T
AD  - Department of Human Genetics, Graduate School of Medicine, The University of 
      Tokyo, Tokyo, Japan.
AD  - Department of Clinical Laboratory Medicine, Faculty of Health Science Technology, 
      Bunkyo Gakuin University, Tokyo, Japan.
FAU - Misawa, Rumi
AU  - Misawa R
AD  - Department of Human Genetics, Graduate School of Medicine, The University of 
      Tokyo, Tokyo, Japan.
AD  - Department of Clinical Laboratory Medicine, Faculty of Health Science Technology, 
      Bunkyo Gakuin University, Tokyo, Japan.
FAU - Shigematsu, Yosuke
AU  - Shigematsu Y
AD  - Department of Pediatrics, Faculty of Medical Sciences, University of Fukui, 
      Fukui, Japan.
FAU - Kuwano, Ryozo
AU  - Kuwano R
AD  - Department of Molecular Genetics, Center for Bioresources, Brain Research 
      Institute, Niigata University, Niigata, Japan.
FAU - Sasaki, Tsukasa
AU  - Sasaki T
AD  - Department of Physical and Health Education, Graduate School of Education, The 
      University of Tokyo, Tokyo, Japan.
FAU - Ishigooka, Jun
AU  - Ishigooka J
AD  - Institute of CNS Pharmacology, Tokyo, Japan.
FAU - Wada, Yuji
AU  - Wada Y
AD  - Department of Neuropsychiatry, Faculty of Medical Sciences, University of Fukui, 
      Fukui, Japan.
FAU - Tsuruta, Kazuhito
AU  - Tsuruta K
AD  - Department of Neurology, Junwakai Memorial Hospital, Miyazaki, Japan.
FAU - Chiba, Shigeru
AU  - Chiba S
AD  - Department of Psychiatry and Neurology, Asahikawa Medical University, Hokkaido, 
      Japan.
FAU - Tanaka, Fumiaki
AU  - Tanaka F
AD  - Department of Neurology and Stroke Medicine, Yokohama City University Graduate 
      School of Medicine, Kanagawa, Japan.
FAU - Yamada, Naoto
AU  - Yamada N
AD  - Department of Psychiatry, Shiga University of Medical Science, Shiga, Japan.
FAU - Okawa, Masako
AU  - Okawa M
AD  - Department of Sleep Medicine, Shiga University of Medical Science, Shiga, Japan.
AD  - Japan Foundation for Neuroscience and Mental Health, Tokyo, Japan.
AD  - Department of Somnology, Tokyo Medical University, Tokyo, Japan.
FAU - Kuroda, Kenji
AU  - Kuroda K
AD  - Department of Psychiatry, Hannan Hospital, Osaka, Japan.
FAU - Kume, Kazuhiko
AU  - Kume K
AD  - Sleep Center, Kuwamizu Hospital, Kumamoto, Japan.
AD  - Department of Stem Cell Biology, Institute of Molecular Genetics and Embryology, 
      Kumamoto University, Kumamoto, Japan.
AD  - Department of Neuropharmacology, Graduate School of Pharmaceutical Sciences, 
      Nagoya City University, Aichi, Japan.
FAU - Hirata, Koichi
AU  - Hirata K
AD  - Department of Neurology, Dokkyo Medical University, Tochigi, Japan.
FAU - Uchimura, Naohisa
AU  - Uchimura N
AD  - Department of Neuropsychiatry, Kurume University School of Medicine, Fukuoka, 
      Japan.
FAU - Shimizu, Tetsuo
AU  - Shimizu T
AD  - Department of Neuropsychiatry, Akita University School of Medicine, Akita, Japan.
AD  - International Institute for Integrative Sleep Medicine (WPI-IIIS), University of 
      Tsukuba, Ibaraki, Japan.
FAU - Inoue, Yuichi
AU  - Inoue Y
AD  - Department of Somnology, Tokyo Medical University, Tokyo, Japan.
AD  - Yoyogi Sleep Disorder Center, Tokyo, Japan.
FAU - Honda, Yutaka
AU  - Honda Y
AD  - Seiwa Hospital, Neuropsychiatric Research Institute, Tokyo, Japan.
FAU - Mishima, Kazuo
AU  - Mishima K
AD  - Department of Neuropsychiatry, Akita University School of Medicine, Akita, Japan.
AD  - International Institute for Integrative Sleep Medicine (WPI-IIIS), University of 
      Tsukuba, Ibaraki, Japan.
AD  - Department of Sleep-Wake Disorders, National Institute of Mental Health, National 
      Center of Neurology and Psychiatry, Tokyo, Japan.
FAU - Honda, Makoto
AU  - Honda M
AD  - Sleep Disorders Project, Department of Psychiatry and Behavioral Sciences, Tokyo 
      Metropolitan Institute of Medical Science, Tokyo, Japan.
AD  - Seiwa Hospital, Neuropsychiatric Research Institute, Tokyo, Japan.
FAU - Tokunaga, Katsushi
AU  - Tokunaga K
AD  - Department of Human Genetics, Graduate School of Medicine, The University of 
      Tokyo, Tokyo, Japan.
LA  - eng
GR  - 22133008/Japan Society for the Promotion of Science (JSPS)/
GR  - 23689022/Japan Society for the Promotion of Science (JSPS)/
GR  - 15H04709/Japan Society for the Promotion of Science (JSPS)/
GR  - 22133008/Japan Society for the Promotion of Science (JSPS)/
GR  - 17ek0109208h0001/Japan Agency for Medical Research and Development (AMED)/
GR  - 17ek0109208h0001/Japan Agency for Medical Research and Development (AMED)/
PT  - Clinical Trial
PT  - Journal Article
PT  - Multicenter Study
DEP - 20180928
PL  - England
TA  - J Hum Genet
JT  - Journal of human genetics
JID - 9808008
RN  - 0 (HLA-DQ beta-Chains)
RN  - 0 (HLA-DQB1 antigen)
RN  - EC 2.3.1.7 (Carnitine O-Acetyltransferase)
SB  - IM
MH  - Carnitine O-Acetyltransferase/*genetics
MH  - Chromosomes, Human, Pair 9/*genetics
MH  - Disorders of Excessive Somnolence/enzymology/*genetics
MH  - Female
MH  - Genome-Wide Association Study
MH  - HLA-DQ beta-Chains/*genetics
MH  - Humans
MH  - Male
MH  - *Polymorphism, Single Nucleotide
EDAT- 2018/09/30 06:00
MHDA- 2018/12/24 06:00
CRDT- 2018/09/30 06:00
PHST- 2018/07/01 00:00 [received]
PHST- 2018/09/13 00:00 [accepted]
PHST- 2018/08/29 00:00 [revised]
PHST- 2018/09/30 06:00 [pubmed]
PHST- 2018/12/24 06:00 [medline]
PHST- 2018/09/30 06:00 [entrez]
AID - 10.1038/s10038-018-0518-8 [pii]
AID - 10.1038/s10038-018-0518-8 [doi]
PST - ppublish
SO  - J Hum Genet. 2018 Dec;63(12):1259-1267. doi: 10.1038/s10038-018-0518-8. Epub 2018 
      Sep 28.