دورية أكاديمية
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: | 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. |
| 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. |
| سنة النشر: | 2021 |
| المجموعة: | IRIS Università degli Studi di Bologna (CRIS - Current Research Information System) |
| مصطلحات موضوعية: | Bipolar disorder, Birth difficultie, GWAS, Hypersomnia, Kleine-Levin syndrome, Cytokine, Disorders of Excessive Somnolence, Female, Genetic Association Studie, Genetic Predisposition to Disease, Human, Male, Obstetric Labor Complication, Odds Ratio, Polymorphism, Genetic, Pregnancy, Risk Assessment, Risk Factor, Disease Susceptibility, Genetic Variation |
| 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. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | ELETTRONICO |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/33737391; info:eu-repo/semantics/altIdentifier/wos/WOS:000631868600003; volume:118; issue:12; firstpage:e2005753118; lastpage:e2005753118; numberofpages:11; journal:PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA; http://hdl.handle.net/11585/859863Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85103146380 |
| DOI: | 10.1073/PNAS.2005753118 |
| الإتاحة: | https://doi.org/10.1073/PNAS.2005753118Test http://hdl.handle.net/11585/859863Test |
| رقم الانضمام: | edsbas.25FC49BF |
| قاعدة البيانات: | BASE |
| DOI: | 10.1073/PNAS.2005753118 |
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