气候变化领域集成服务门户(CCPortal): Kleine-Levin syndrome is associated with birth difficulties and genetic variants in the TRANK1 gene loci

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DOI	10.1073/PNAS.2005753118
	Kleine-Levin syndrome is associated with birth difficulties and genetic variants in the TRANK1 gene loci
	Ambati A.; Hillary R.; Leu-Semenescu S.; Ollila H.M.; Lin L.; During E.H.; Farber N.; Rico T.J.; Faraco J.; Leary E.; Goldstein-Piekarski A.N.; Huang Y.-S.; Han F.; Sivan Y.; Lecendreux M.; Dodet P.; Honda M.; Gadoth N.; Nevsimalova S.; Pizza F.; Kanbayashi T.; Peraita-Adrados R.; Leschziner G.D.; Hasan R.; Canellas F.; Kume K.; Daniilidou M.; Bourgin P.; Rye D.; Vicario J.L.; Hogl B.; Hong S.C.; Plazzi G.; Mayer G.; Landtblom A.M.; Dauvilliers Y.; Arnulf I.; Mignot E.J.-M.
发表日期	2021
ISSN	00278424
卷号	118 期号:12
英文摘要	Kleine-Levin syndrome (KLS) is a rare disorder characterized by severe episodic hypersomnia, with cognitive impairment accompanied by apathy or disinhibition. Pathophysiology is unknown, although imaging studies indicate decreased activity in hypothalamic/thalamic areas during episodes. Familial occurrence is increased, and risk is associated with reports of a difficult birth. We conducted a worldwide case.control genome-wide association study in 673 KLS cases collected over 14 y, and ethnically matched 15,341 control individuals. We found a strong genome-wide significant association (rs71947865, Odds Ratio [OR] = 1.48, P = 8.6 × 10-9) within the 3'region of TRANK1 gene locus, previously associated with bipolar disorder and schizophrenia. Strikingly, KLS cases with rs71947865 variant had significantly increased reports of a difficult birth. As perinatal outcomes have dramatically improved over the last 40 y, we further stratified our sample by birth years and found that recent cases had a significantly reduced rs71947865 association. While the rs71947865 association did not replicate in the entire follow-up sample of 171 KLS cases, rs71947865 was significantly associated with KLS in the subset follow-up sample of 59 KLS cases who reported birth difficulties (OR = 1.54, P = 0.01). Genetic liability of KLS as explained by polygenic risk scores was increased (pseudo R2= 0.15; P < 2.0 ∼ 10-22at P = 0.5 threshold) in the follow-up sample. Pathway analysis of genetic associations identified enrichment of circadian regulation pathway genes in KLS cases. Our results suggest links between KLS, circadian regulation, and bipolar disorder, and indicate that the TRANK1 polymorphisms in conjunction with reported birth difficulties may predispose to KLS. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Bipolar disorder; Birth difficulties; GWAS; Hypersomnia; Kleine-Levin syndrome
语种	英语
scopus关键词	Article; bipolar disorder; case control study; circadian rhythm; controlled study; disease association; female; gene; gene locus; gene mutation; genetic association; genetic predisposition; genetic risk score; genetic variability; genome-wide association study; genotype environment interaction; human; hypersomnia; major clinical study; pathophysiology; pregnancy disorder; priority journal; single nucleotide polymorphism; TRANK1 gene
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180208
作者单位	Center for Sleep Sciences and Medicine, Stanford University School of Medicine, Palo Alto, CA 94304, United States; Sleep Disorders, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris-Sorbonne, National Reference Center for Narcolepsy, Idiopathic Hypersomnia and Kleine-Levin Syndrome, Sorbonne University, Institut Hospitalo, Universitaire A Institut du Cerveau et de la Moelle, Paris, F-75013, France; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, United States; Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, United States; Kleine-Levin Syndrome Foundation, Boston, MA 02468, United States; Sierra-Pacific Mental Illness Research, Education, and Clinical Center, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA 94304, United States; Department of Child Psychiatry, Chang Gung Memorial Hospital and University, Taoyuan, 33305, Taiwan; Sleep Center, Chang Gung Memorial Hospital and University, T...
推荐引用方式 GB/T 7714	Ambati A.,Hillary R.,Leu-Semenescu S.,et al. Kleine-Levin syndrome is associated with birth difficulties and genetic variants in the TRANK1 gene loci[J],2021,118(12).
APA	Ambati A..,Hillary R..,Leu-Semenescu S..,Ollila H.M..,Lin L..,...&Mignot E.J.-M..(2021).Kleine-Levin syndrome is associated with birth difficulties and genetic variants in the TRANK1 gene loci.Proceedings of the National Academy of Sciences of the United States of America,118(12).
MLA	Ambati A.,et al."Kleine-Levin syndrome is associated with birth difficulties and genetic variants in the TRANK1 gene loci".Proceedings of the National Academy of Sciences of the United States of America 118.12(2021).