@article{1e790488bd264d04a4cc0f08f6118b44,
title = "Analysis of shared common genetic risk between amyotrophic lateral sclerosis and epilepsy",
abstract = "Because hyper-excitability has been shown to be a shared pathophysiological mechanism, we used the latest and largest genome-wide studies in amyotrophic lateral sclerosis (n = 36,052) and epilepsy (n = 38,349) to determine genetic overlap between these conditions. First, we showed no significant genetic correlation, also when binned on minor allele frequency. Second, we confirmed the absence of polygenic overlap using genomic risk score analysis. Finally, we did not identify pleiotropic variants in meta-analyses of the 2 diseases. Our findings indicate that amyotrophic lateral sclerosis and epilepsy do not share common genetic risk, showing that hyper-excitability in both disorders has distinct origins.",
keywords = "ALS, Amyotrophic Lateral Sclerosis/genetics, Epilepsy/genetics, Gene Frequency, Genetic Variation, Genetic correlation, Genome-Wide Association Study, Humans, Negative Results, Risk",
author = "Dick Schijven and Remi Stevelink and Mark McCormack and {van Rheenen}, Wouter and Luykx, {Jurjen J.} and Koeleman, {Bobby P.C.} and Veldink, {Jan H.} and Kevin Kenna",
note = "Funding Information: We thank the members of the Project MinE ALS GWAS Consortium and the International League Against Epilepsy Consortium on Complex Epilepsies for their contributions (see Supplementary Information for detailed lists of consortium members). This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement n° 772376 - EScORIAL. The collaboration project is co-funded by the PPP Allowance made available by Health~Holland, Top Sector Life Sciences & Health, to stimulate public-private partnerships. Funding Information: This study was supported by a Marie-Curie Individual Fellowship (number 751761) from the European Commission, and NIH grant P01-AG-032953. This project has furthermore received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement no 772376 – EScORIAL). This is in part an EU Joint Program - Neurodegenerative Disease Research (JPND) project. The project is also supported through the following funding organizations under the aegis of JPND ( www.jpnd.eu ): United Kingdom, Medical Research Council (MR/L501529/1, MR/R024804/1); the Netherlands, ZONMW (grant no. 733051071); and through the Motor Neurone Disease Association. This study represents independent research part funded by the National Institute for Health Research (NIHR) Maudsley Biomedical Research Centre. Samples used in this research were in part obtained from the UK National DNA Bank for MND Research, funded by the MND Association and the Wellcome Trust. We would like to thank people with MND and their families for their participation in this project. Funding Information: We thank the members of the Project MinE ALS GWAS Consortium and the International League Against Epilepsy Consortium on Complex Epilepsies for their contributions (see Supplementary Information for detailed lists of consortium members). This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement n° 772376 - EScORIAL. The collaboration project is co-funded by the PPP Allowance made available by Health~Holland, Top Sector Life Sciences & Health, to stimulate public-private partnerships. Publisher Copyright: {\textcopyright} 2020 The Author(s)",
year = "2020",
month = aug,
doi = "10.1016/j.neurobiolaging.2020.04.011",
language = "English",
volume = "92",
pages = "153.e1--153.e5",
journal = "Neurobiology of Aging",
issn = "0197-4580",
publisher = "Elsevier",
}