Journal article
Application of rare variant transmission disequilibrium tests to epileptic encephalopathy trio sequence data
European journal of human genetics : EJHG, v 25(7), pp 894-899
01 Jun 2017
PMID: 28513609
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The classic epileptic encephalopathies, including infantile spasms (IS) and Lennox-Gastaut syndrome (LGS), are severe seizure disorders that usually arise sporadically. De novo variants in genes mainly encoding ion channel and synaptic proteins have been found to account for over 15% of patients with IS or LGS. The contribution of autosomal recessive genetic variation, however, is less well understood. We implemented a rare variant transmission disequilibrium test (TDT) to search for autosomal recessive epileptic encephalopathy genes in a cohort of 320 outbred patient-parent trios that were generally prescreened for rare metabolic disorders. In the current sample, our rare variant transmission disequilibrium test did not identify individual genes with significantly distorted transmission over expectation after correcting for the multiple tests. While the rare variant transmission disequilibrium test did not find evidence of a role for individual autosomal recessive genes, our current sample is insufficiently powered to assess the overall role of autosomal recessive genotypes in an outbred epileptic encephalopathy population.
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Details
- Title
- Application of rare variant transmission disequilibrium tests to epileptic encephalopathy trio sequence data
- Creators
- Andrew S. Allen - Biostat (United States)Samuel F. Berkovic - The University of MelbourneJoshua Bridgers - Columbia UniversityPatrick Cossette - Université de MontréalDennis Dlugos - College Station Medical CenterMichael P. Epstein - Emory UniversityTracy GlauserDavid B. Goldstein - Imperial Coll London, Ctr Clin Translat, Div Brain Sci, London, EnglandErin L. Heinzen - Columbia UniversityYu Jiang - Biostat (United States)Michael R. Johnson - Imperial Coll London, Ctr Clin Translat, Div Brain Sci, London, EnglandRuben Kuzniecky - College Station Medical CenterDaniel H. Lowenstein - Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USAAnthony G. Marson - University of LiverpoolHeather C. Mefford - University of WashingtonTerence J. O'Brien - College Station Medical CenterRuth Ottman - Columbia UniversitySteven Petrou - College Station Medical CenterSlave Petrovski - The University of MelbourneAnnapurna Poduri - Boston Childrens Hosp, Dept Neurol, Div Epilepsy & Clin Neurophysiol, Boston, MA USAZhong Ren - Columbia UniversityIngrid E. Scheffer - The University of MelbourneElliott Sherr - Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USAQuanli Wang - Columbia UniversityRudi Balling - University of LuxembourgNina Barisic - University of ZagrebStephanie Baulac - Sorbonne UniversitéHande Caglayan - Boğaziçi UniversityDana Craiu - College Station Medical CenterPeter De Jonghe - VIB, Neurogenet Grp, Dept Mol Genet, Antwerp, BelgiumChristel Depienne - Université de StrasbourgRenzo Guerrini - University of FlorenceIngo Helbig - Christian-Albrechts-Universität zu KielHelle Hjalgrim - Danish Epilepsy Ctr, Dianalund, DenmarkDorota Hoffman-Zacharska - College Station Medical CenterJohanna Jaehn - Christian-Albrechts-Universität zu KielKarl Martin Klein - Goethe University FrankfurtBobby Koeleman - College Station Medical CenterVladimir Komarek - College Station Medical CenterRoland Krause - University of LuxembourgEric Leguern - Sorbonne UniversitéAnna-Elina Lehesjoki - University of HelsinkiJohannes R. Lemke - Univ Leipzig Hosp & Clin, Inst Human Genet, Leipzig, GermanyHolger Lerche - University of TübingenTarja Linnankivi - University of HelsinkiCarla Marini - University of FlorencePatrick May - University of LuxembourgRikke S. Moller - Danish Epilepsy Ctr, Dianalund, DenmarkHiltrud Muhle - Christian-Albrechts-Universität zu KielDeb Pal - Kings Coll London, Inst Psychiat, Dept Clin Neurosci, London, EnglandAarno Palotie - Wellcome Sanger InstituteFelix Rosenow - Goethe University FrankfurtKaja Selmer - College Station Medical CenterJose M. Serratosa - College Station Medical CenterSanjay Sisodiya - UCL Inst Neurol, Dept Clin & Expt Epilepsy, London, EnglandUlrich Stephani - Christian-Albrechts-Universität zu KielKatalin Sterbova - College Station Medical CenterPasquale Striano - University of GenoaArvid Suls - VIB, Neurogenet Grp, Dept Mol Genet, Antwerp, BelgiumTiina Talvik - University of TartuSarah von Spiczak - Christian-Albrechts-Universität zu KielYvonne Weber - University of TübingenSarah Weckhuysen - VIB, Neurogenet Grp, Dept Mol Genet, Antwerp, BelgiumFederico Zara - University of GenoaBassel Abou-Khalil - Vanderbilt UniversityBrian K. Alldredge - UCSF Sch Pharm, Dept Clin Pharm, San Francisco, CA USADina Amrom - Montreal Neurol Hosp & Inst, Neurogenet Unit, Montreal, PQ, CanadaEva Andermann - Montreal Neurol Hosp & Inst, Neurogenet Unit, Montreal, PQ, CanadaFrederick Andermann - Montreal Neurol Hosp & Inst, Epilepsy Res Grp, Montreal, PQ, CanadaJocelyn F. Bautista - College Station Medical CenterSamuel F. Berkovic - The University of MelbourneJudith Bluvstein - College Station Medical CenterGregory D. Cascino - Mayo Clin, Div Epilepsy, Rochester, MN USADamian Consalvo - Ramos Mejia Hosp, Neurol Div, Epilepsy Ctr, Buenos Aires, DF, ArgentinaPatricia Crumrine - University of PittsburghOrrin Devinsky - College Station Medical CenterDennis Dlugos - College Station Medical CenterMichael P. Epstein - Emory UniversityMiguel E. Fiol - University of MinnesotaNathan B. Fountain - University of VirginiaJacqueline French - NYU, Comprehens Epilepsy Ctr, New York, NY USADaniel Friedman - College Station Medical CenterTracy Glauser - College Station Medical CenterKevin Haas - Vanderbilt UniversitySheryl R. Haut - The Bronx DefendersJean Hayward - Kaiser PermanenteSucheta Joshi - Univ Michigan, Pediat & Communicable Dis, Ann Arbor, MI 48109 USAAndres Kanner - University of MiamiHeidi E. Kirsch - Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USAEric H. Kossoff - Johns Hopkins UniversityRachel Kuperman - Childrens Hosp & Res Ctr Oakland, Epilepsy Program, Oakland, CA USARuben Kuzniecky - College Station Medical CenterDaniel H. Lowenstein - Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USAShannon M. McGuire - Childrens Hosp Epilepsy Ctr New Orleans, Clin Neurol, New Orleans, LA USAPaul V. Motika - Oregon Hlth & Sci Univ, Comprehens Epilepsy Ctr, Portland, OR 97201 USAEdward J. Novotny - University of WashingtonRuth Ottman - Columbia UniversityJuliann M. Paolicchi - College Station Medical CenterJack Parent - College Station Medical CenterKristen Park - College Station Medical CenterAnnapurna Poduri - Boston Childrens Hosp, Dept Neurol, Div Epilepsy & Clin Neurophysiol, Boston, MA USAIngrid E. Scheffer - The University of MelbourneRenee A. Shellhaas - Univ Michigan, Pediat Neurol, Ann Arbor, MI 48109 USAElliott Sherr - Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USAJoseph Sirven - Mayo Clin, Dept Neurol, Scottsdale, AZ USAMichael C. Smith - Rush UniversityJoseph Sullivan - Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USALiu Lin Thio - College Station Medical CenterAnu Venkat - Brunswick (United States)Eileen P. G. Vining - Johns Hopkins UniversityGretchen K. Von Allmen - College Station Medical CenterJudith L. Weisenberg - College Station Medical CenterPeter Widdess-Walsh - Beaumont Hosp & Royal Coll Surg, Dept Neurol, Dublin, IrelandMelodie R. Winawer - Columbia UniversityEpi4K Consortium
- Publication Details
- European journal of human genetics : EJHG, v 25(7), pp 894-899
- Publisher
- Springer Nature
- Number of pages
- 6
- Grant note
- 141549 / Academy of Finland (AKA); Research Council of Finland; Finnish Funding Agency for Technology & Innovation (TEKES) U19AI067854; UM1-AI100645 / National Institute of Allergy and Infectious Diseases Center P30 AG028377 / Bryan ADRC NIA German Society for Epileptology (DGfE) DFG: HE5415/3-1; Le1030/111; RO3396/2-1 / German Research Foundation; German Research Foundation (DFG) intramural funds of the University of Kiel MR/N026063/1 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) SNF: 32EP30_136042/1 / Swiss National Science Foundation; Swiss National Science Foundation (SNSF) Foundation noepilep. 09805 / Wellcome Trust Richard Thalheimer Philanthropic Fund Duke Chancellor's Discovery Program Research Fund Biogen Idec.; Biogen Andrew's Foundation AG-NS-044108 / Ellison Medical Foundation New Scholar award; Lawrence Ellison Foundation K01MH098126; R01MH097993 / National Institute of Mental Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH) ANR-10IAIHU-06 / program 'Investissements d'avenir'; Agence Nationale de la Recherche (ANR) Fund for Scientific Research Flanders (FWO); FWO 1R56AI098588-01A1 / National Institute of Allergy and Infectious Diseases; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) Finding a Cure for Epilepsy and Seizures MR/N026063/1 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) Eurocores program EuroEPINOMICS-RES of the European Science Foundation Folkhalsan Research Foundation HL-102923; HL-102924; HL-102925; HL-102926; HL-103010 / NHLBI; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) Division of Intramural Research; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA M11-074 / B57 SAIC-Fredrick Inc N602531 / European Union through Seventh Framework Programme (FP7) under the project DESIRE DFG Cluster of Excellence 'Inflammation at Interfaces' and 'Future Ocean' IonNeurONet: 01GM1105 / Federal Ministry for Education and Research; Federal Ministry of Education & Research (BMBF) 141549 / Academy of Finland; Research Council of Finland 01EY1103 / Popgen 2.0 network (P2N) through the German Ministry for Education and Research Bill and Melinda Gates Foundation; Bill & Melinda Gates Foundation NS053998; Epi4K NS077364; NS077274; NS077303; NS077276 / National Institute of Neurological Disorders and Stroke; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Medicine (Graduate); Urban Health Collaborative
- Web of Science ID
- WOS:000403061300020
- Scopus ID
- 2-s2.0-85019562360
- Other Identifier
- 991021838141904721
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- Domestic collaboration
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- Web of Science research areas
- Biochemistry & Molecular Biology
- Genetics & Heredity