Kleine-Levin syndrome is associated with birth difficulties and genetic variants in the TRANK1 gene loci
| العنوان: | Kleine-Levin syndrome is associated with birth difficulties and genetic variants in the TRANK1 gene loci |
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| المؤلفون: | Natan Gadoth, Birgit Högl, Rosa Hasan, G. Plazzi, Andrea N. Goldstein-Piekarski, Makrina Daniilidou, Thomas J Rico, Smaranda Leu-Semenescu, Ryan P. Hillary, Neal M. Farber, Guy D. Leschziner, Emmanuel Mignot, Yakov Sivan, Michel Lecendreux, José L. Vicario, Hanna Ollila, Juliette Faraco, Sona Nevsimalova, Isabelle Arnulf, Fang Han, Francesca Canellas, Pauline Dodet, Patrice Bourgin, Geert Mayer, Fabio Pizza, Makoto Honda, Yu-Shu Huang, Kazuhiko Kume, Rosa Peraita-Adrados, Ling Lin, David B. Rye, Takashi Kanbayashi, Eileen B. Leary, Seung Chul Hong, Emmanuel H. During, Anne-Marie Landtblom, Yves Dauvilliers, Aditya Ambati |
| المساهمون: | 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., Retiveau, Nolwenn, Stanford University, Service de Pathologies du sommeil [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre National de Référence pour les Maladies Rares : narcolepsie, hypersomnie idiopathique et syndrome de Kleine-Levin [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Veterans Affairs Palo Alto Healthcare System, Chang Gung Memorial Hospital [Taipei] (CGMH), Peking University [Beijing], Sackler Faculty of Medicine, Tel Aviv University (TAU), Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Tokyo Metropolitan Institute of Medical Science (TMIMS), Tel Aviv Sourasky Medical Center [Te Aviv], Charles University [Prague] (CU), University of Bologna/Università di Bologna, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Université de Tsukuba = University of Tsukuba, Hospital General Universitario 'Gregorio Marañón' [Madrid], Guy's Hospital [London], King‘s College London, Universidade de São Paulo = University of São Paulo (USP), Nagoya City University [Nagoya, Japan], Uppsala University Hospital, Linköping university hospital, CHU Strasbourg, Emory University [Atlanta, GA], Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Catholic University of Korea, Philipps Universität Marburg = Philipps University of Marburg, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM) |
| المصدر: | Proceedings of the National Academy of Sciences of the United States of America Proceedings of the National Academy of Sciences of the United States of America, 2021, 118 (12), pp.e2005753118. ⟨10.1073/pnas.2005753118⟩ |
| بيانات النشر: | Proceedings of the National Academy of Sciences, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, Pediatrics, Bipolar Disorder, [SDV]Life Sciences [q-bio], Genome-wide association study, MESH: Risk Assessment, MESH: Pregnancy, MESH: Risk Factors, Pregnancy, MESH: Bipolar Disorder, Birth difficultie, Odds Ratio, GWAS, Apathy, MESH: Genetic Variation, Obstetric Labor Complication, MESH: Genetic Association Studies, MESH: Cytokines, Hypersomnia, Multidisciplinary, MESH: Genetic Predisposition to Disease, Pathophysiology, [SDV] Life Sciences [q-bio], Schizophrenia, Female, Disease Susceptibility, medicine.symptom, MESH: Kleine-Levin Syndrome, Human, medicine.medical_specialty, MESH: Obstetric Labor Complications, MESH: Disease Susceptibility, Birth difficulties, Disorders of Excessive Somnolence, Genetic Association Studie, Kleine-Levin Syndrome, Risk Assessment, MESH: Polymorphism, Genetic, medicine, Genetic Predisposition to Disease, Bipolar disorder, Cytokine, MESH: Humans, Polymorphism, Genetic, business.industry, Risk Factor, Genetic Variation, Odds ratio, medicine.disease, MESH: Male, MESH: Odds Ratio, Kleine–Levin syndrome, Kleine-Levin syndrome, bipolar disorder, birth difficulties, hypersomnia, Disinhibition, business, MESH: Female, MESH: Disorders of Excessive Somnolence |
| الوصف: | 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. |
| وصف الملف: | ELETTRONICO |
| تدمد: | 1091-6490 0027-8424 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a628f3bc4473a79bda8966a1c1b669c7Test https://doi.org/10.1073/pnas.2005753118Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....a628f3bc4473a79bda8966a1c1b669c7 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10916490 00278424 |
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