Genome-wide mega-analysis identifies 16 loci and highlights diverse biological mechanisms in the common epilepsies

Grants

Funding Acknowledgements

We are grateful to the patients and volunteers who participated in this research. We thank the following clinicians and research scientists for their contribution through sample collection (cases and controls), data analysis, and project support: Geka Ackerhans, Muna Alwaidh, R E Appleton, Willem Frans Arts, Guiliano Avanzini, Paul Boon, Sarah Borror, Kees Braun, Oebele Brouwer, Hans Carpay, Karen Carter, Peter Cleland, Oliver C Cockerell, Paul Cooper, Celia Cramp, Emily de los Reyes, Chris French, Catharine Freyer, William Gallentine, Michel Georges, Peter Goulding, Micheline Gravel, Rhian Gwilliam, Lori Hamiwka, Steven J Howell, Adrian Hughes, Aatif Husain, Monica Islam, Floor Jansen, Mary Karn, Mark Kellett, Ditte B Kjelgaard, Karl Martin Klein, Donna Kring, Annie WC Kung, Mark Lawden, Jo Ellen Lee, Benjamin Legros, Leanne Lehwald, Edouard Louis, Colin HT Lui, Zelko Matkovic, Jennifer McKinney, Brendan McLean, Mohamad Mikati, Bethanie Morgan-Followell, Wim Van Paesschen, Anup Patel, Manuela Pendziwiat, Marcus Reuber, Richard Roberts, Guy Rouleau, Cathy Schumer, B Sharack, Kevin Shianna, NC Sin, Saurabh Sinha, Laurel Slaughter, Sally Steward, Deborah Terry, Chang-Yong Tsao, TH Tsoi, Patrick Tugendhaft, Jaime-Dawn Twanow, Jorge Vidaurre, Sarah Weckhuysen, Pedro Weisleder, Kathleen White, Virginia Wong, Raju Yerra, Jacqueline Yinger and all contributing clinicians from the Department of Clinical and Experimental Epilepsy at the National Hospital for Neurology and Neurosurgery and UCL Institute of Neurology. Data generated as part of the EPIGEN Consortium was included in this study. We would like to thank Dr. Weihua Meng (University of Dundee), Dr. Mark Adams (University of Edinburgh) and Dr. Ynte Ruigrok (UMC Utrecht), Dr. Bjarke Feenstra (Statens Serum Institut, Denmark), Dr. Risto Kayanne (Institute for Molecular Medicine Finland) and the International Headache Genetics Consortium for providing GWAS summary statistics for their respective cohorts. Ischemic stroke summary statistics were accessed through the ISGC Cerebrovascular Disease Knowledge Portal. We would like to thank Dr. Weihua Meng (University of Dundee), Dr. Mark Adams (University of Edinburgh) and Dr. Ynte Ruigrok (UMC Utrecht), Dr. Bjarke Feenstra (Statens Serum Institut, Denmark), Dr. Risto Kayanne (Institute for Molecular Medicine Finland), and the International Headache Genetics Consortium for providing GWAS summary statistics for their respective cohorts. We would like to thank the Ming Fund for providing funding for Re. St. M.McC. has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 751761. This work was in part supported by an award by a Translational Research Scholars award from the Health Research Board of Ireland (C.D.W.), by research grants from Science Foundation Ireland (SFI) (16/RC/3948 and X) and co-funded under the European Regional Development Fund and by FutureNeuro industry partners. Further funding sources include: Wellcome Trust (grant 084730); Epilepsy Society, UK, NIHR (08-08-SCC); GIHE: NIH R01-NS-49306-01 (R.J.B.); NIH R01-NS-053998 (D.H.L); GSCFE: NIH R01-NS-064154-01 (R.J.B. and Ha.Ha.); NIH: UL1TR001070, Development Fund from The Children's Hospital of Philadelphia (Ha. Ha.); NHMRC Program Grant ID: 1091593 (S.F.B., I.E.S., K.L.O., and K.E.B.); The Royal Melbourne Hospital Foundation Lottery Grant (S.P.); The RMH Neuroscience Foundation (T.J.O'B.); European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement no 279062 (EpiPGX) and 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 (Th.Sa.), WE4896/3-1); EuroEPINOMICS Consortium (European Science Foundation/DFG: SA434/5-1, NU50/8-1, LE1030/11-1, HE5415/3-1 (Th.Sa., P.N., H.L., I.H.), RO 3396/2-1); the German Federal Ministry of Education and Research, National Genome Research Network (NGFNplus/EMINet: 01GS08120, and 01GS08123 (Th.Sa., H.L.); IntenC, TUR 09/I10 (Th.Sa.)); The Netherlands National Epilepsy Fund (grant 04-08); EC (FP7 project EpiPGX 279062). Research Grants Council of the Hong Kong Special Administrative Region, China project numbers HKU7623/08M (S.S.C, P.K., L.W.B., P.C.S), HKU7747/07M (S.S.C., P.C.S.) and CUHK4466/06M (P.K., L.B). Collection of Belgian cases was supported by the Fonds National de la Recherche Scientifique, Fondation Erasme, Universite Libre de Bruxelles. GlaxoSmithKline funded the recruitment and data collection for the GenEpA Consortium samples. We acknowledge the support of Nationwide Children's hospital in Columbus, Ohio, USA. The Wellcome Trust (WT066056) and The NIHR Biomedical Research Centres Scheme (P31753) supported UK contributions. Further support was received through the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (Contract: N01HD33348). The project was also supported by the popgen 2.0 network through a grant from the German Ministry for Education and Research (01EY1103). Parts of the analysis of this work were performed on resources of the High Performance Center of the University of Luxembourg and Elixir-Luxembourg. The KORA study was initiated and financed by the Helmholtz Zentrum Munchen - German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria. Furthermore, KORA research was supported within the Munich Center of Health Sciences (MC-Health), Ludwig-Maximilians-Universitat, as part of LMUinnovativ. The International League Against Epilepsy (ILAE) facilitated the Consortium through the Commission on Genetics and by financial support; however, the opinions expressed in the manuscript do not necessarily represent the policy or position of the ILAE.