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

Stevelink, Remi; Campbell, Ciarán; Chen, Siwei; Abou‐Khalil, Bassel; Adesoji, Oluyomi M.; Afawi, Zaid; Amadori, Elisabetta; Anderson, Alison; Anderson, Joseph; Andrade, Danielle M.; Annesi, Grazia; Auce, Pauls; Avberšek, Andreja; Bahlo, Melanie; Baker, Mark D.; Balagura, Ganna; Balestrini, Simona; Barba, Carmen; Barboza, Karen; Bartoloméi, Fabrice; Bast, Thomas; Baum, Larry; Baumgartner, Tobias; Baykan, Betül; Bebek, Nerses; Becker, Albert J.; Becker, Felicitas; Bennett, Caitlin A.; Berghuis, Bianca; Berkovic, Samuel F.; Beydoun, Ahmad; Bianchini, Claudia; Bisulli, Francesca; Blatt, Ilan; Bobbili, Dheeraj Reddy; Borggraefe, Ingo; Boßelmann, Christian M.; Braatz, Vera; Bradfield, Jonathan P.; Brockmann, Knut; Brody, Lawrence C.; Buono, Russell J.; Busch, Robyn M.; Çağlayan, Hande; Campbell, Ellen; Canafoglia, Laura; Canavati, Christina; Cascino, Gregory D.; Castellotti, Barbara; Catarino, Claudia B.; Cavalleri, Gianpiero L.; Cerrato, Felecia; Chassoux, Francine; Cherny, Stacey S.; Cheung, Ching‐Lung; Chinthapalli, Krishna; Chou, I‐Jun; Chung, Seo‐Kyung; Churchhouse, Claire; Clark, Peggy O.; Cole, Andrew J.; Compston, Alastair; Coppola, Antonietta; Cosico, Mahgenn; Cossette, Patrick; Craig, John; Cusick, Caroline; Daly, Mark J.; Davis, Lea K.; Haan, Gerrit‐Jan de; Delanty, Norman; Depondt, Chantal; Derambure, Philippe; Devinsky, Orrin; Vito, Lidia Di; Dlugos, Dennis; Doccini, Viola; Doherty, Colin P.; El-Naggar, Hany; Elger, Christian E.; Ellis, Colin A.; Eriksson, Johan G.; Faucon, Annika; Feng, Yen‐Chen Anne; Ferguson, Lisa; Ferraro, Thomas N.; Ferri, Lorenzo; Feucht, Martha; Fitzgerald, Mark P.; Fonferko‐Shadrach, Beata; Fortunato, Francesco; Franceschetti, Silvana; Franke, Andre; French, Jacqueline A.; Freri, Elena; Gagliardi, Monica; Gambardella, Antonio; Geller, Eric B.; Giangregorio, Tania; Gjerstad, Leif; Glauser, Tracy A.; Goldberg, Ethan M.; Goldman, Alicia; Granata, Tiziana; Greenberg, David A.; Guerrini, Renzo; Gupta, Namrata; Haas, Kevin F.; Håkonarson, Håkon; Hallmann, Kerstin; Hassanin, Emadeldin; Hegde, Manu; Heinzen, Erin L.; Helbig, Ingo; Hengsbach, Christian; Heyne, Henrike; Hirose, Shinichi; Hirsch, Édouard; Hjalgrim, Helle; Howrigan, Daniel P.; Hucks, Donald; Hung, Po‐Cheng; Iacomino, Michele; Imbach, Lukas; Inoue, Yushi; Ishii, Atsushi; Jamnadas-Khoda, Jennifer; Jehi, Lara; Johnson, Michael R.; Kälviäinen, Reetta; Kamatani, Yoichiro; Kanaan, Moien; Kanai, Masahiro; Kantanen, Anne-Mari; Kara, Bülent; Kariuki, Symon M.; Kasperavičiūtė, Dalia; Trenité, Dorothée Kasteleijn‐Nolst; Kato, Mitsuhiro; Kegele, Josua; Kesim, Yeşim; Zgheib, Nathalie K.; King, Chontelle; Kirsch, Heidi E.; Klein, Karl Martin; Kluger, Gerhard; Knake, Susanne; Knowlton, Robert C.; Koeleman, Bobby P.C.; Korczyn, Amos D.; Koupparis, Andreas; Kousiappa, Ioanna; Krause, Roland; Krenn, Martin; Krestel, Heinz; Krey, Ilona; Kunz, Wolfram S.; Kurki, Mitja; Kurlemann, Gerhard; Kuzniecky, Ruben; Kwan, Patrick; Labate, Angelo; Lacey, Austin; Lal, Dennis; Landoulsi, Zied; Lau, YL; Lauxmann, Stephen; Leech, Stephanie L.; Lehesjoki, Anna‐Elina; Lemke, Johannes R.; Lerche, Holger; Lesca, Gaëtan; Leu, Costin; Lewin, Naomi; Lewis‐Smith, David; Li, Gloria Hoi‐Yee; Li, Qingqin S.; Licchetta, Laura; Lin, Kuang-Lin; Lindhout, Dick; Linnankivi, Tarja; Lopes‐Cendes, Íscia; Lowenstein, Daniel H.; Lui, Colin H. 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doi:10.1038/s41588-023-01485-w

reviewNature GeneticsAug 31, 2023HYBRID OA

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

RSRemi Stevelink CCCiarán Campbell SCSiwei Chen BABassel Abou‐Khalil OMOluyomi M. Adesoji

University Medical Center Utrecht · Royal College of Surgeons in Ireland · +201 more institutions

PubMed

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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…

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Topics & keywords

Topics

Keywords

Genetic architecture
Genome-wide association study
Biology
Epilepsy
Genetics
Heritability
Genetic association
SNP

UN Sustainable Development Goals

Good health and well-being

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