PMID- 38469065
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240313
IS  - 1446-9235 (Print)
IS  - 1479-8425 (Electronic)
IS  - 1446-9235 (Linking)
VI  - 20
IP  - 1
DP  - 2022 Jan
TI  - Genome-wide association study of idiopathic hypersomnia in a Japanese population.
PG  - 137-148
LID - 10.1007/s41105-021-00349-2 [doi]
AB  - Idiopathic hypersomnia (IH) is a rare sleep disorder characterized by excessive 
      daytime sleepiness, great difficulty upon awakening, and prolonged sleep time. In 
      contrast to narcolepsy type 1, which is a well-recognized hypersomnia, the 
      etiology of IH remains poorly understood. No susceptibility loci for IH have been 
      identified, although familial aggregations have been observed among patients with 
      IH. Narcolepsy type 1 is strongly associated with human leukocyte antigen 
      (HLA)-DQB1*06:02; however, no significant associations between IH and HLA alleles 
      have been reported. To identify genetic variants that affect susceptibility to 
      IH, we performed a genome-wide association study (GWAS) and two replication 
      studies involving a total of 414 Japanese patients with IH and 6587 healthy 
      Japanese individuals. A meta-analysis of the three studies found no 
      single-nucleotide polymorphisms (SNPs) that reached the genome-wide significance 
      level. However, we identified several candidate SNPs for IH. For instance, a 
      common genetic variant (rs2250870) within an intron of PDE9A was suggestively 
      associated with IH. rs2250870 was significantly associated with expression levels 
      of PDE9A in not only whole blood but also brain tissues. The leading SNP in the 
      PDE9A region was the same in associations with both IH and PDE9A expression. 
      PDE9A is a potential target in the treatment of several brain diseases, such as 
      depression, schizophrenia, and Alzheimer's disease. It will be necessary to 
      examine whether PDE9A inhibitors that have demonstrated effects on 
      neurophysiologic and cognitive function can contribute to the development of new 
      treatments for IH, as higher expression levels of PDE9A were observed with regard 
      to the risk allele of rs2250870. The present study constitutes the first GWAS of 
      genetic variants associated with IH. A larger replication study will be required 
      to confirm these associations. SUPPLEMENTARY INFORMATION: The online version 
      contains supplementary material available at 10.1007/s41105-021-00349-2.
CI  - (c) The Author(s), under exclusive licence to Japanese Society of Sleep Research 
      2021.
FAU - Tanida, Kotomi
AU  - Tanida K
AD  - Department of Human Genetics, Graduate School of Medicine, The University of 
      Tokyo, Tokyo, Japan. GRID: grid.26999.3d. ISNI: 0000 0001 2151 536X
FAU - Shimada, Mihoko
AU  - Shimada M
AD  - Department of Human Genetics, Graduate School of Medicine, The University of 
      Tokyo, Tokyo, Japan. GRID: grid.26999.3d. ISNI: 0000 0001 2151 536X
AD  - Sleep Disorders Project, Department of Psychiatry and Behavioral Sciences, Tokyo 
      Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, 
      Tokyo, 156-8506 Japan. GRID: grid.272456.0. ISNI: 0000 0000 9343 3630
AD  - Genome Medical Science Project (Toyama), National Center for Global Health and 
      Medicine, Tokyo, Japan. GRID: grid.45203.30. ISNI: 0000 0004 0489 0290
FAU - Khor, Seik-Soon
AU  - Khor SS
AD  - Department of Human Genetics, Graduate School of Medicine, The University of 
      Tokyo, Tokyo, Japan. GRID: grid.26999.3d. ISNI: 0000 0001 2151 536X
AD  - Genome Medical Science Project (Toyama), National Center for Global Health and 
      Medicine, Tokyo, Japan. GRID: grid.45203.30. ISNI: 0000 0004 0489 0290
FAU - Toyoda, Hiromi
AU  - Toyoda H
AD  - Department of Human Genetics, Graduate School of Medicine, The University of 
      Tokyo, Tokyo, Japan. GRID: grid.26999.3d. ISNI: 0000 0001 2151 536X
FAU - Kato, Kayoko
AU  - Kato K
AD  - Department of Human Genetics, Graduate School of Medicine, The University of 
      Tokyo, Tokyo, Japan. GRID: grid.26999.3d. ISNI: 0000 0001 2151 536X
FAU - Kotorii, Nozomu
AU  - Kotorii N
AD  - Department of Neuropsychiatry, Kurume University School of Medicine, Fukuoka, 
      Japan. GRID: grid.410781.b. ISNI: 0000 0001 0706 0776
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 - Kato, Takao
AU  - Kato T
AD  - Department of Neuropsychiatry, Kurume University School of Medicine, Fukuoka, 
      Japan. GRID: grid.410781.b. ISNI: 0000 0001 0706 0776
FAU - Hiejima, Hiroshi
AU  - Hiejima H
AD  - Department of Neuropsychiatry, Kurume University School of Medicine, Fukuoka, 
      Japan. GRID: grid.410781.b. ISNI: 0000 0001 0706 0776
FAU - Ozone, Motohiro
AU  - Ozone M
AD  - Department of Neuropsychiatry, Kurume University School of Medicine, Fukuoka, 
      Japan. GRID: grid.410781.b. ISNI: 0000 0001 0706 0776
FAU - Uchimura, Naohisa
AU  - Uchimura N
AD  - Department of Neuropsychiatry, Kurume University School of Medicine, Fukuoka, 
      Japan. GRID: grid.410781.b. ISNI: 0000 0001 0706 0776
FAU - Ikegami, Azusa
AU  - Ikegami A
AD  - Sleep Center, Kuwamizu Hospital, Kumamoto, 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. GRID: grid.274841.c. ISNI: 0000 0001 0660 
      6749
AD  - Department of Neuropharmacology, Graduate School of Pharmaceutical Sciences, 
      Nagoya City University, Aichi, Japan. GRID: grid.260433.0. ISNI: 0000 0001 0728 
      1069
FAU - Kanbayashi, Takashi
AU  - Kanbayashi T
AD  - International Institute for Integrative Sleep Medicine (WPI-IIIS), University of 
      Tsukuba, Ibaraki, Japan. GRID: grid.20515.33. ISNI: 0000 0001 2369 4728
AD  - Ibaraki Prefectural Medical Center of Psychiatry, Ibaraki, Japan.
FAU - Imanishi, Aya
AU  - Imanishi A
AD  - Department of Neuropsychiatry, Akita University Graduate School of Medicine, 
      Akita, Japan. GRID: grid.251924.9. ISNI: 0000 0001 0725 8504
FAU - Kamei, Yuichi
AU  - Kamei Y
AD  - Department of Laboratory Medicine, National Center Hospital, National Center of 
      Neurology and Psychiatry, Tokyo, Japan. GRID: grid.419280.6. ISNI: 0000 0004 1763 
      8916
AD  - Kamisuwa Hospital, Nagano, 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. GRID: grid.416859.7. ISNI: 0000 
      0000 9832 2227
FAU - Wada, Yamato
AU  - Wada Y
AD  - Department of Psychiatry, Hannan Hospital, Osaka, Japan.
FAU - Kuroda, Kenji
AU  - Kuroda K
AD  - Department of Psychiatry, Hannan Hospital, Osaka, Japan.
FAU - Miyamoto, Masayuki
AU  - Miyamoto M
AD  - Department of Neurology, Dokkyo Medical University, Tochigi, Japan. GRID: 
      grid.255137.7. ISNI: 0000 0001 0702 8004
FAU - Hirata, Koichi
AU  - Hirata K
AD  - Department of Neurology, Dokkyo Medical University, Tochigi, Japan. GRID: 
      grid.255137.7. ISNI: 0000 0001 0702 8004
FAU - Takami, Masanori
AU  - Takami M
AD  - Department of Psychiatry, Shiga University of Medical Science, Shiga, Japan. 
      GRID: grid.410827.8. ISNI: 0000 0000 9747 6806
FAU - Yamada, Naoto
AU  - Yamada N
AD  - Department of Psychiatry, Shiga University of Medical Science, Shiga, Japan. 
      GRID: grid.410827.8. ISNI: 0000 0000 9747 6806
FAU - Okawa, Masako
AU  - Okawa M
AD  - Department of Sleep Medicine, Shiga University of Medical Science, Shiga, Japan. 
      GRID: grid.410827.8. ISNI: 0000 0000 9747 6806
AD  - Japan Foundation for Neuroscience and Mental Health, Tokyo, Japan.
AD  - Department of Somnology, Tokyo Medical University, Tokyo, Japan. GRID: 
      grid.410793.8. ISNI: 0000 0001 0663 3325
FAU - Omata, Naoto
AU  - Omata N
AD  - Department of Nursing, Faculty of Health Science, Fukui Health Science 
      University, Fukui, Japan.
AD  - Department of Neuropsychiatry, Faculty of Medical Sciences, University of Fukui, 
      Fukui, Japan. GRID: grid.163577.1. ISNI: 0000 0001 0692 8246
FAU - Kondo, Hideaki
AU  - Kondo H
AD  - International Institute for Integrative Sleep Medicine (WPI-IIIS), University of 
      Tsukuba, Ibaraki, Japan. GRID: grid.20515.33. ISNI: 0000 0001 2369 4728
FAU - Kodama, Tohru
AU  - Kodama T
AD  - Sleep Disorders Project, Department of Psychiatry and Behavioral Sciences, Tokyo 
      Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, 
      Tokyo, 156-8506 Japan. GRID: grid.272456.0. ISNI: 0000 0000 9343 3630
FAU - Inoue, Yuichi
AU  - Inoue Y
AD  - Department of Somnology, Tokyo Medical University, Tokyo, Japan. GRID: 
      grid.410793.8. ISNI: 0000 0001 0663 3325
AD  - Yoyogi Sleep Disorder Center, Neuropsychiatric Research Institute, Tokyo, Japan. 
      GRID: grid.419280.6. ISNI: 0000 0004 1763 8916
FAU - Mishima, Kazuo
AU  - Mishima K
AD  - International Institute for Integrative Sleep Medicine (WPI-IIIS), University of 
      Tsukuba, Ibaraki, Japan. GRID: grid.20515.33. ISNI: 0000 0001 2369 4728
AD  - Department of Neuropsychiatry, Akita University Graduate School of Medicine, 
      Akita, Japan. GRID: grid.251924.9. ISNI: 0000 0001 0725 8504
AD  - Department of Sleep-Wake Disorders, National Institute of Mental Health, National 
      Center of Neurology and Psychiatry, Tokyo, Japan. GRID: grid.416859.7. ISNI: 0000 
      0000 9832 2227
FAU - Honda, Makoto
AU  - Honda M
AD  - Sleep Disorders Project, Department of Psychiatry and Behavioral Sciences, Tokyo 
      Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, 
      Tokyo, 156-8506 Japan. GRID: grid.272456.0. ISNI: 0000 0000 9343 3630
AD  - Seiwa Hospital, Neuropsychiatric Research Institute, Tokyo, Japan. GRID: 
      grid.419280.6. ISNI: 0000 0004 1763 8916
FAU - Tokunaga, Katsushi
AU  - Tokunaga K
AD  - Department of Human Genetics, Graduate School of Medicine, The University of 
      Tokyo, Tokyo, Japan. GRID: grid.26999.3d. ISNI: 0000 0001 2151 536X
AD  - Genome Medical Science Project (Toyama), National Center for Global Health and 
      Medicine, Tokyo, Japan. GRID: grid.45203.30. ISNI: 0000 0004 0489 0290
FAU - Miyagawa, Taku
AU  - Miyagawa T
AUID- ORCID: 0000-0002-9466-9420
AD  - Department of Human Genetics, Graduate School of Medicine, The University of 
      Tokyo, Tokyo, Japan. GRID: grid.26999.3d. ISNI: 0000 0001 2151 536X
AD  - Sleep Disorders Project, Department of Psychiatry and Behavioral Sciences, Tokyo 
      Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, 
      Tokyo, 156-8506 Japan. GRID: grid.272456.0. ISNI: 0000 0000 9343 3630
LA  - eng
PT  - Journal Article
DEP - 20211012
PL  - Japan
TA  - Sleep Biol Rhythms
JT  - Sleep and biological rhythms
JID - 101199488
PMC - PMC10899960
OTO - NOTNLM
OT  - Genome-wide association study (GWAS)
OT  - Idiopathic hypersomnia
OT  - Phosphodiesterase
OT  - Single-nucleotide polymorphisms (SNPs)
OT  - Sleep
COIS- Conflict of interestDr. Inoue Yuichi has received grants and payment for 
      lectures, including service on speakers' bureaus, and has provided expert 
      testimony for MSD K.K., Takeda Pharmaceutical Co. Ltd., and Eisai Co. Ltd. Dr. 
      Makoto Honda has received consulting fees from Takeda Pharmaceutical Co. Ltd. The 
      other authors have no competing interests to declare.
EDAT- 2021/10/12 00:00
MHDA- 2021/10/12 00:01
PMCR- 2022/10/12
CRDT- 2024/03/12 03:49
PHST- 2021/06/04 00:00 [received]
PHST- 2021/09/20 00:00 [accepted]
PHST- 2021/10/12 00:01 [medline]
PHST- 2021/10/12 00:00 [pubmed]
PHST- 2024/03/12 03:49 [entrez]
PHST- 2022/10/12 00:00 [pmc-release]
AID - 349 [pii]
AID - 10.1007/s41105-021-00349-2 [doi]
PST - epublish
SO  - Sleep Biol Rhythms. 2021 Oct 12;20(1):137-148. doi: 10.1007/s41105-021-00349-2. 
      eCollection 2022 Jan.