PMID- 27305985
OWN - NLM
STAT- MEDLINE
DCOM- 20170406
LR  - 20181113
IS  - 1435-232X (Electronic)
IS  - 1434-5161 (Linking)
VI  - 61
IP  - 10
DP  - 2016 Oct
TI  - Evaluation of polygenic risks for narcolepsy and essential hypersomnia.
PG  - 873-878
LID - 10.1038/jhg.2016.65 [doi]
AB  - In humans, narcolepsy is a sleep disorder that is characterized by sleepiness, 
      cataplexy and rapid eye movement (REM) sleep abnormalities. Essential hypersomnia 
      (EHS) is another type of sleep disorder that is characterized by excessive 
      daytime sleepiness without cataplexy. A human leukocyte antigen (HLA) class II 
      allele, HLA-DQB1*06:02, is a major genetic factor for narcolepsy. Almost all 
      narcoleptic patients are carriers of this HLA allele, while 30-50% of EHS 
      patients and 12% of all healthy individuals in Japan carry this allele. The 
      pathogenesis of narcolepsy and EHS is thought to be partially shared. To evaluate 
      the contribution of common single-nucleotide polymorphisms (SNPs) to narcolepsy 
      onset and to assess the common genetic background of narcolepsy and EHS, we 
      conducted a polygenic analysis that included 393 narcoleptic patients, 38 EHS 
      patients with HLA-DQB1*06:02, 119 EHS patients without HLA-DQB1*06:02 and 1582 
      healthy individuals. We also included 376 individuals with panic disorder and 213 
      individuals with autism to confirm whether the results were biased. Polygenic 
      risks in narcolepsy were estimated to explain 58.1% (P(HLA-DQB1*06:02)=2.30 x 
      10(-48), P(whole genome without HLA-DQB1*06:02)=6.73 x 10(-2)) including 
      HLA-DQB1*06:02 effects and 1.3% (P(whole genome without HLA-DQB1*06:02)=2.43 x 
      10(-2)) excluding HLA-DQB1*06:02 effects. The results also indicated that 
      small-effect SNPs contributed to the development of narcolepsy. Reported 
      susceptibility SNPs for narcolepsy in the Japanese population, CPT1B (carnitine 
      palmitoyltransferase 1B), TRA@ (T-cell receptor alpha) and P2RY11 (purinergic 
      receptor P2Y, G-protein coupled, 11), were found to explain 0.8% of narcolepsy 
      onset (P(whole genome without HLA-DQB1*06:02)=9.74 x 10(-2)). EHS patients with 
      HLA-DQB1*06:02 were estimated to have higher shared genetic background to 
      narcoleptic patients than EHS patients without HLA-DQB1*06:02 even when the 
      effects of HLA-DQB1*06:02 were excluded (EHS with HLA-DQB1*06:02: 40.4%, 
      P(HLA-DQB1*06:02)=7.02 x 10(-)(14), P(whole genome without HLA-DQB1*06:02)=1.34 x 
      10(-)(1), EHS without HLA-DQB1*06:02: 0.4%, P(whole genome without 
      HLA-DQB1*06:02)=3.06 x 10(-)(1)). Meanwhile, the polygenic risks for narcolepsy 
      could not explain the onset of panic disorder and autism, suggesting that our 
      results were reasonable.
FAU - Yamasaki, Maria
AU  - Yamasaki M
AD  - Department of Human Genetics, Graduate School of Medicine, The University of 
      Tokyo, Tokyo, Japan.
FAU - Miyagawa, Taku
AU  - Miyagawa T
AD  - Department of Human Genetics, Graduate School of Medicine, The University of 
      Tokyo, Tokyo, Japan.
AD  - Sleep Disorders Project, Department of Psychiatry and Behavioral Sciences, Tokyo 
      Metropolitan Institute of Medical Science, Tokyo, Japan.
FAU - Toyoda, Hiromi
AU  - Toyoda H
AD  - Department of Human Genetics, Graduate School of Medicine, The University of 
      Tokyo, Tokyo, Japan.
FAU - Khor, Seik-Soon
AU  - Khor SS
AD  - Department of Human Genetics, Graduate School of Medicine, The University of 
      Tokyo, Tokyo, Japan.
FAU - Liu, Xiaoxi
AU  - Liu X
AD  - Laboratory for Genotyping Development, Center for Genomic Medicine, RIKEN, 
      Kanagawa, Japan.
FAU - Kuwabara, Hitoshi
AU  - Kuwabara H
AD  - Department of Child Psychiatry, Graduate School of Medicine, The University of 
      Tokyo, Tokyo, Japan.
FAU - Kano, Yukiko
AU  - Kano Y
AD  - Department of Child Psychiatry, Graduate School of Medicine, The University of 
      Tokyo, Tokyo, Japan.
FAU - Shimada, Takafumi
AU  - Shimada T
AD  - Division for Counseling and Support, The University of Tokyo, Tokyo, Japan.
FAU - Sugiyama, Toshiro
AU  - Sugiyama T
AD  - Department of Child and Adolescent Psychiatry, Hamamatsu University School of 
      Medicine, Shizuoka, Japan.
FAU - Nishida, Hisami
AU  - Nishida H
AD  - Asunaro Hospital for Child and Adolescent Psychiatry, Mie, Japan.
FAU - Sugaya, Nagisa
AU  - Sugaya N
AD  - Department of Epidemiology and Public Health, Yokohama City University Graduate 
      school of Medicine, Kanagawa, Japan.
FAU - Tochigi, Mamoru
AU  - Tochigi M
AD  - Teikyo University Hospital, Tokyo, Japan.
FAU - Otowa, Takeshi
AU  - Otowa T
AD  - Department of Neuropsychiatry, Graduate School of Medicine, The University of 
      Tokyo, Tokyo, Japan.
FAU - Okazaki, Yuji
AU  - Okazaki Y
AD  - Tokyo Metropolitan Matsuzawa Hospital, Tokyo, Japan.
FAU - Kaiya, Hisanobu
AU  - Kaiya H
AD  - Panic Disorder Research Center, Warakukai Med Corp, Tokyo, Japan.
FAU - Kawamura, Yoshiya
AU  - Kawamura Y
AD  - Department of Psychiatry, Shonan Kamakura General Hospital, Kanagawa, Japan.
FAU - Miyashita, Akinori
AU  - Miyashita A
AD  - Department of Molecular Genetics, Bioresource Science Branch, Center for 
      Bioresources, Brain Research Institute, Niigata University, Niigata, Japan.
FAU - Kuwano, Ryozo
AU  - Kuwano R
AD  - Department of Molecular Genetics, Bioresource Science Branch, Center for 
      Bioresources, Brain Research Institute, Niigata University, Niigata, Japan.
FAU - Kasai, Kiyoto
AU  - Kasai K
AD  - Department of Neuropsychiatry, Graduate School of Medicine, The University of 
      Tokyo, Tokyo, Japan.
FAU - Tanii, Hisashi
AU  - Tanii H
AD  - Department of Psychiatry, Graduate School of Medicine, Mie University, Mie, 
      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 - Honda, Yutaka
AU  - Honda Y
AD  - Japan Somnology Center, Neuropsychiatric Research Institute, 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  - Japan Somnology Center, 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
PT  - Journal Article
DEP - 20160616
PL  - England
TA  - J Hum Genet
JT  - Journal of human genetics
JID - 9808008
RN  - 0 (HLA-DQ beta-Chains)
RN  - 0 (HLA-DQB1 antigen)
SB  - IM
MH  - Alleles
MH  - Comparative Genomic Hybridization
MH  - Disorders of Excessive Somnolence/diagnosis/*genetics
MH  - *Genetic Association Studies
MH  - *Genetic Predisposition to Disease
MH  - Genotype
MH  - HLA-DQ beta-Chains/genetics
MH  - Humans
MH  - *Multifactorial Inheritance
MH  - Narcolepsy/diagnosis/*genetics
MH  - Phenotype
MH  - Polymorphism, Single Nucleotide
MH  - Risk
EDAT- 2016/10/26 06:00
MHDA- 2017/04/07 06:00
CRDT- 2016/06/17 06:00
PHST- 2015/11/23 00:00 [received]
PHST- 2016/04/21 00:00 [revised]
PHST- 2016/04/28 00:00 [accepted]
PHST- 2016/10/26 06:00 [pubmed]
PHST- 2017/04/07 06:00 [medline]
PHST- 2016/06/17 06:00 [entrez]
AID - jhg201665 [pii]
AID - 10.1038/jhg.2016.65 [doi]
PST - ppublish
SO  - J Hum Genet. 2016 Oct;61(10):873-878. doi: 10.1038/jhg.2016.65. Epub 2016 Jun 16.