A variant at 9q34.11 is associated with HLA-DQB1*06:02 negative essential hypersomnia View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2018-09-28

AUTHORS

Taku Miyagawa, Seik-Soon Khor, Hiromi Toyoda, Takashi Kanbayashi, Aya Imanishi, Yohei Sagawa, Nozomu Kotorii, Tatayu Kotorii, Yu Ariyoshi, Yuji Hashizume, Kimihiro Ogi, Hiroshi Hiejima, Yuichi Kamei, Akiko Hida, Masayuki Miyamoto, Azusa Ikegami, Yamato Wada, Masanori Takami, Yuichi Higashiyama, Ryoko Miyake, Hideaki Kondo, Yota Fujimura, Yoshiyuki Tamura, Yukari Taniyama, Naoto Omata, Yuji Tanaka, Shunpei Moriya, Hirokazu Furuya, Mitsuhiro Kato, Yoshiya Kawamura, Takeshi Otowa, Akinori Miyashita, Hiroto Kojima, Hiroh Saji, Mihoko Shimada, Maria Yamasaki, Takumi Kobayashi, Rumi Misawa, Yosuke Shigematsu, Ryozo Kuwano, Tsukasa Sasaki, Jun Ishigooka, Yuji Wada, Kazuhito Tsuruta, Shigeru Chiba, Fumiaki Tanaka, Naoto Yamada, Masako Okawa, Kenji Kuroda, Kazuhiko Kume, Koichi Hirata, Naohisa Uchimura, Tetsuo Shimizu, Yuichi Inoue, Yutaka Honda, Kazuo Mishima, Makoto Honda, Katsushi Tokunaga

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. More... »

PAGES

1259-1267

References to SciGraph publications

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  • Journal

    TITLE

    Journal of Human Genetics

    ISSUE

    12

    VOLUME

    63

    Author Affiliations

  • Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
  • International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Ibaraki, Japan
  • Department of Neuropsychiatry, Akita University School of Medicine, Akita, Japan
  • Kotorii Isahaya Hospital, Nagasaki, Japan
  • Ariyoshi Sleep Clinic, Fukuoka, Japan
  • Department of Neuropsychiatry, Kurume University School of Medicine, Fukuoka, Japan
  • Department of Laboratory Medicine, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan
  • Department of Sleep-Wake Disorders, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan
  • Department of Neurology, Dokkyo Medical University, Tochigi, Japan
  • Sleep Center, Kuwamizu Hospital, Kumamoto, Japan
  • Department of Psychiatry, Hannan Hospital, Osaka, Japan
  • Department of Psychiatry, Shiga University of Medical Science, Shiga, Japan
  • Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine, Kanagawa, Japan
  • Center for Sleep Medicine, Saiseikai Nagasaki Hospital, Nagasaki, Japan
  • Department of Psychiatry, Tokyo Medical University Hachioji Medical Center, Tokyo, Japan
  • Department of Psychiatry and Neurology, Asahikawa Medical University, Hokkaido, Japan
  • Department of Neurology, Junwakai Memorial Hospital, Miyazaki, Japan
  • Department of Neuropsychiatry, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
  • Department of Psychiatry, Tokyo Women’s Medical University School of Medicine, Tokyo, Japan
  • Department of Neurology, Kochi Medical School, Kochi University, Kochi, Japan
  • Department of Pediatrics, Showa University School of Medicine, Tokyo, Japan
  • Department of Psychiatry, Shonan Kamakura General Hospital, Kanagawa, Japan
  • Graduate School of Clinical Psychology, Teikyo Heisei University Major of Professional Clinical Psychology, Tokyo, Japan
  • Department of Molecular Genetics, Center for Bioresources, Brain Research Institute, Niigata University, Niigata, Japan
  • HLA Foundation Laboratory, Kyoto, Japan
  • Department of Clinical Laboratory Medicine, Faculty of Health Science Technology, Bunkyo Gakuin University, Tokyo, Japan
  • Department of Pediatrics, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
  • Department of Physical and Health Education, Graduate School of Education, The University of Tokyo, Tokyo, Japan
  • Institute of CNS Pharmacology, Tokyo, Japan
  • Department of Somnology, Tokyo Medical University, Tokyo, Japan
  • Department of Neuropharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Aichi, Japan
  • Yoyogi Sleep Disorder Center, Tokyo, Japan
  • Seiwa Hospital, Neuropsychiatric Research Institute, Tokyo, Japan
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s10038-018-0518-8

    DOI

    http://dx.doi.org/10.1038/s10038-018-0518-8

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1107304083

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30266950


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