期刊
NATURE COMMUNICATIONS
卷 9, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-018-07524-z
关键词
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资金
- Ming Fund
- European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant [751761]
- Translational Research Scholars award from the Health Research Board of Ireland
- Science Foundation Ireland (SFI) [16/RC/3948]
- European Regional Development Fund
- FutureNeuro industry partners
- Wellcome Trust [084730]
- Epilepsy Society, UK, NIHR [08-08-SCC]
- GIHE: NIH [R01-NS-49306-01]
- NIH [R01-NS-053998, UL1TR001070]
- GSCFE: NIH [R01-NS-064154-01]
- The Children's Hospital of Philadelphia
- NHMRC Program [1091593]
- Royal Melbourne Hospital Foundation Lottery Grant
- RMH Neuroscience Foundation
- European Union's Seventh Framework Programme (FP7/2007-2013) [279062, 602102]
- Department of Health's NIHR Biomedical Research Centers funding scheme
- European Community (EC: FP6 project EPICURE) [LSHM-CT2006-037315]
- German Research Foundation (DFG) [SA434/4-1/4-26-1, WE4896/3-1]
- EuroEPINOMICS Consortium (European Science Foundation/DFG) [SA434/5-1, NU50/8-1, LE1030/11-1, HE5415/3-1, RO 3396/2-1]
- German Federal Ministry of Education and Research
- National Genome Research Network [01GS08120, 01GS08123, TUR 09/I10]
- Netherlands National Epilepsy Fund [04-08]
- EC (FP7 project) [EpiPGX 279062]
- Research Grants Council of the Hong Kong Special Administrative Region, China [HKU7623/08M, HKU7747/07M, CUHK4466/06M]
- Fonds National de la Recherche Scientifique
- Fondation Erasme
- Universite Libre de Bruxelles
- GlaxoSmithKline
- Nationwide Children's hospital in Columbus, Ohio, USA
- The Wellcome Trust [WT066056]
- NIHR Biomedical Research Centres Scheme [P31753]
- Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development [N01HD33348]
- popgen 2.0 network through a grant from the German Ministry for Education and Research [01EY1103]
- Helmholtz Zentrum Munchen - German Research Center for Environmental Health - German Federal Ministry of Education and Research (BMBF)
- State of Bavaria
- Munich Center of Health Sciences (MC-Health)
- Ludwig-Maximilians-Universitat
- MRC [G0800637] Funding Source: UKRI
- Marie Curie Actions (MSCA) [751761] Funding Source: Marie Curie Actions (MSCA)
The epilepsies affect around 65 million people worldwide and have a substantial missing heritability component. We report a genome-wide mega-analysis involving 15,212 individuals with epilepsy and 29,677 controls, which reveals 16 genome-wide significant loci, of which 11 are novel. Using various prioritization criteria, we pinpoint the 21 most likely epilepsy genes at these loci, with the majority in genetic generalized epilepsies. These genes have diverse biological functions, including coding for ion-channel subunits, transcription factors and a vitamin-B6 metabolism enzyme. Converging evidence shows that the common variants associated with epilepsy play a role in epigenetic regulation of gene expression in the brain. The results show an enrichment for monogenic epilepsy genes as well as known targets of antiepileptic drugs. Using SNP-based heritability analyses we disentangle both the unique and overlapping genetic basis to seven different epilepsy subtypes. Together, these findings provide leads for epilepsy therapies based on underlying pathophysiology.
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