GWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture

Grants

Funding Acknowledgements

Some of the data reported in this study were collected as part of a project undertaken by the ILAE and some of the authors are experts selected by the ILAE. Opinions expressed by the authors, however, do not necessarily represent the policy or position of the ILAE. This study received support from Science Foundation Ireland (SFI; 16/RC/3948), cofunded under the European Regional Development Fund, the Research Unit FOR-2715 of the German Research Foundation (MN: NO755/6-1 and NO755/13-1), from Wellcome Trust (grant 084730), European Union's Seventh Framework Program (FP7/2007-2013) under grant agreement 279062 (EpiPGX), The Muir Maxwell Trust and the Epilepsy Society, UK and Fonds National de la Recherche Luxembourg (Research Unit FOR-2715, FNR grant INTER/DFG/21/16394868 MechEPI2) to P.M. and R. Krause. Part of this work was undertaken at University College London Hospitals, which received a proportion of funding from the NIHR Biomedical Research Centers funding scheme. Further support was received by a 'Vrienden WKZ' fund 1616091 (MING) to R. Stevelink and B.P.C.K., a National Health and Medical Research Council (NHMRC) of Australia Program Grant (1091593) to S.F.B. and I.E.S. and an NHMRC Investigator grant (APP1195236) to M.B. The Australian Government Research Training Program Scholarship (APP533086) provided by the Australian Commonwealth Government and the University of Melbourne supports K.L.O., a Wellcome Clinical Ph.D. Fellowship on the 4Ward North program (203914/Z/16/Z) supported D.L.-S., the UKRI MRC award MR/S02638X/1 and the NIHR Imperial Biomedical Research Center (BRC) support M.R.J., and Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), Brazil (grant 2013/07559-3) supported I.L.-C. The funding bodies had no role in the study design, data collection, analysis and interpretation, or in writing the manuscript. We thank the Epi25 principal investigators, local staff from individual cohorts and all patients with epilepsy who participated in research studies at local centers for making possible this global collaboration and resource to advance epilepsy genetics research. We thank the Epi25 principal investigators, local staff from individual cohorts and all patients with epilepsy who participated in research studies at local centers for making possible this global collaboration and resource to advance epilepsy genetics research. This work is part of the Centers for Common Disease Genomics (CCDG) program, funded by the National Human Genome Research Institute (NHGRI), The Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Heart, Lung and Blood Institute (NHLBI). CCDG-funded Epi25 research activities at the Broad Institute, including genomic data generation in the Broad Genomics Platform, were supported by NHGRI grant UM1 HG008895 (PIs: E. Lander, S. Gabriel, M. Daly, S. Kathiresan). The Genome Sequencing Program efforts were also supported by NHGRI under grant 5U01HG009088-02. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. We thank the Stanley Center for Psychiatric Research at the Broad Institute for supporting the genomic data generation efforts as well as the aggregation of control samples and cohorts to contribute to the Epi25 GWAS analyses. In particular, the Genomic Psychiatry Cohort controls were genotyped on the GSA-MD v1.r 0 by the Broad Genomics Platform with funding from NIH grant U01MH105641 and the Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard. The FINRISK controls were part of the FINRISK studies supported by the THL (formerly KTL: National Public Health Institute) through budgetary funds from the government, with additional funding from institutions such as the Academy of Finland, the European Union, ministries and national and international foundations and societies to support specific research purposes. The collection of the Hong Kong Osteoporosis Study (HKOS) control samples was funded by the Bone Health Fund and Research Grants Council-Early Career Scheme (project 27100416). Other control datasets included IBD NIDDK and samples from the Mass General Brigham (MGB) Biobank available from dbGaP under study accession number phs002018.v1.p1. We acknowledge the participants and investigators of the FinnGen study. The FinnGen project is funded by two grants from Business Finland (HUS 4685/31/2016 and UH 4386/31/2016) and the following industry partners: AbbVie, AstraZeneca UK, Biogen MA, Bristol Myers Squibb (and Celgene Corporation & Celgene International II Sarl), Genentech, Merck Sharp & Dohme Corp,Pfizer, GlaxoSmithKline Intellectual Property Development, Sanofi US Services, Maze Therapeutics, Janssen Biotech, Novartis AG and Boehringer Ingelheim. The following biobanks are acknowledged for delivering biobank samples to FinnGen: Auria Biobank (www.auria.fi/biopankki), THL Biobank (www.thl.fi/biobank), Helsinki Biobank (www.helsinginbiopankki.fi), Biobank Borealis of Northern Finland (https://www.ppshp.fi/Tutkimus-ja-opetus/Biopankki/Pages/Biobank-Borealis-briefly-in-English.aspx), Finnish Clinical Biobank Tampere (www.tays.fi/en-US/Research_and_development/Finnish_Clinical_Biobank_Tampere), Biobank of Eastern Finland (www.ita-suomenbiopankki.fi/en), Central Finland Biobank (www.ksshp.fi/fi-FI/Potilaalle/Biopankki), Finnish Red Cross Blood Service Biobank (www.veripalvelu.fi/verenluovutus/biopankkitoiminta) and Terveystalo Biobank (www.terveystalo.com/fi/Yritystietoa/Terveystalo-Biopankki/Biopankki/).All Finnish biobanks are members of BBMRI.fi infrastructure (www.bbmri.fi).Finnish Biobank Cooperative-FINBB (https://finbb.fi/)-is the coordinator of BBMRI-ERIC operations in Finland. The Finnish biobank data can be accessed through the Fingenious services (https://site.fingenious.fi/en/) managed by FINBB.