@article{24a80f69833040d9ad0ed1b613cc7a37,
title = "GWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture",
abstract = "Epilepsy is a highly heritable disorder affecting over 50 million people worldwide, of which about one-third are resistant to current treatments. Here we report a multi-ancestry genome-wide association study including 29,944 cases, stratified into three broad categories and seven subtypes of epilepsy, and 52,538 controls. We identify 26 genome-wide significant loci, 19 of which are specific to genetic generalized epilepsy (GGE). We implicate 29 likely causal genes underlying these 26 loci. SNP-based heritability analyses show that common variants explain between 39.6% and 90% of genetic risk for GGE and its subtypes. Subtype analysis revealed markedly different genetic architectures between focal and generalized epilepsies. Gene-set analyses of GGE signals implicate synaptic processes in both excitatory and inhibitory neurons in the brain. Prioritized candidate genes overlap with monogenic epilepsy genes and with targets of current antiseizure medications. Finally, we leverage our results to identify alternate drugs with predicted efficacy if repurposed for epilepsy treatment.",
keywords = "Humans, Genome-Wide Association Study, Epilepsy/genetics, Brain, Neurons",
author = "{International League Against Epilepsy Consortium on Complex Epilepsies} and Remi Stevelink and Ciar{\'a}n Campbell and Siwei Chen and Bassel Abou-Khalil and Adesoji, {Oluyomi M.} and Zaid Afawi and Elisabetta Amadori and Alison Anderson and Joseph Anderson and Andrade, {Danielle M.} and Grazia Annesi and Pauls Auce and Andreja Avbersek and Melanie Bahlo and Baker, {Mark D.} and Ganna Balagura and Simona Balestrini and Carmen Barba and Karen Barboza and Fabrice Bartolomei and Thomas Bast and Larry Baum and Tobias Baumgartner and Bet{\"u}l Baykan and Nerses Bebek and Becker, {Albert J.} and Felicitas Becker and Bennett, {Caitlin A.} and Bianca Berghuis and Berkovic, {Samuel F.} and Ahmad Beydoun and Claudia Bianchini and Francesca Bisulli and Ilan Blatt and Bobbili, {Dheeraj R.} and Ingo Borggraefe and Christian Bosselmann and Vera Braatz and Bradfield, {Jonathan P.} and Knut Brockmann and Brody, {Lawrence C.} and Buono, {Russell J.} and Busch, {Robyn M.} and Hande Caglayan and Ellen Campbell and Laura Canafoglia and Christina Canavati and Cascino, {Gregory D.} and Barbara Castellotti and Tsai, {Meng Han}",
note = "{\textcopyright} 2023. The Author(s).",
year = "2023",
month = sep,
doi = "10.1038/s41588-023-01485-w",
language = "英语",
volume = "55",
pages = "1471--1482",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Research",
number = "9",
}