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Evaluation of polygenic risks for narcolepsy and essential hypersomnia
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نویسنده
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Yamasaki Maria ,Miyagawa Taku ,Toyoda Hiromi ,Khor Seik-Soon ,Liu Xiaoxi ,Kuwabara Hitoshi ,Kano Yukiko ,Shimada Takafumi ,Sugiyama Toshiro ,Nishida Hisami ,Sugaya Nagisa ,Tochigi Mamoru ,Otowa Takeshi ,Okazaki Yuji ,Kaiya Hisanobu ,Kawamura Yoshiya ,Miyashita Akinori ,Kuwano Ryozo ,Kasai Kiyoto ,Tanii Hisashi ,Sasaki Tsukasa ,Honda Yutaka ,Honda Makoto ,Tokunaga Katsushi
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منبع
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journal of human genetics - 2016 - دوره : 61 - شماره : 10 - صفحه:873 -878
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چکیده
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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% (phla-dqb1*06:02=2.30 × 10−48, pwhole genome without hla-dqb1*06:02=6.73 × 10−2) including hla-dqb1*06:02 effects and 1.3% (pwhole genome without hla-dqb1*06:02=2.43 × 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 (pwhole genome without hla-dqb1*06:02=9.74 × 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%, phla-dqb1*06:02=7.02 × 10−14, pwhole genome without hla-dqb1*06:02=1.34 × 10−1, ehs without hla-dqb1*06:02: 0.4%, pwhole genome without hla-dqb1*06:02=3.06 × 10−1). meanwhile, the polygenic risks for narcolepsy could not explain the onset of panic disorder and autism, suggesting that our results were reasonable.
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آدرس
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The University of Tokyo, Department of Human Genetics, Japan, The University of Tokyo, Department of Human Genetics, Japan. Tokyo Metropolitan Institute of Medical Science, Department of Psychiatry and Behavioral Sciences, Japan, The University of Tokyo, Department of Human Genetics, Japan, The University of Tokyo, Department of Human Genetics, Japan, Center for Genomic Medicine, Laboratory for Genotyping Development, Japan, The University of Tokyo, Department of Child Psychiatry, Japan, The University of Tokyo, Department of Child Psychiatry, Japan, The University of Tokyo, Division for Counseling and Support, Japan, Hamamatsu University School of Medicine, Department of Child and Adolescent Psychiatry, Japan, Asunaro Hospital for Child and Adolescent Psychiatry, Japan, Yokohama City University Graduate school of Medicine, Department of Epidemiology and Public Health, Japan, Teikyo University Hospital, Japan, The University of Tokyo, Department of Neuropsychiatry, Japan, Tokyo Metropolitan Matsuzawa Hospital, Japan, Panic Disorder Research Center, Japan, Shonan Kamakura General Hospital, Department of Psychiatry, Japan, Niigata University, Bioresource Science Branch, Department of Molecular Genetics, Japan, Niigata University, Bioresource Science Branch, Department of Molecular Genetics, Japan, The University of Tokyo, Department of Neuropsychiatry, Japan, Mie University, Department of Psychiatry, Japan, The University of Tokyo, Department of Physical and Health Education, Japan, Neuropsychiatric Research Institute, Japan, Tokyo Metropolitan Institute of Medical Science, Department of Psychiatry and Behavioral Sciences, Japan. Neuropsychiatric Research Institute, Japan, The University of Tokyo, Department of Human Genetics, Japan
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Authors
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