Polygenic burden in focal and generalized epilepsies
| Title: | Polygenic burden in focal and generalized epilepsies |
|---|---|
| Authors: | Leu C.; Stevelink R.; Smith A. W.; Goleva S. B.; Kanai M.; Ferguson L.; Campbell C.; Kamatani Y.; Okada Y.; Sisodiya S. M.; Cavalleri G. L.; Koeleman B. P. C.; Lerche H.; Jehi L.; Davis L. K.; Najm I. M.; Palotie A.; Daly M. J.; Busch R. M.; Lal D.; Feng Y. -C. A.; Howrigan D. P.; Abbott L. E.; Tashman K.; Cerrato F.; Churchhouse C.; Gupta N.; Neale B. M.; Berkovic S. F.; Goldstein D. B.; Lowenstein D. H.; Cossette P.; Cotsapas C.; De Jonghe P.; Dixon-Salazar T.; Guerrini R.; Hakonarson H.; Heinzen E. L.; Helbig I.; Kwan P.; Marson A. G.; Petrovski S.; Kamalakaran S.; Stewart R.; Weckhuysen S.; Depondt C.; Dlugos D. J.; Scheffer I. E.; Striano P.; Freyer C.; Krause R.; May P.; McKenna K.; Regan B. M.; Bellows S. T.; Bennett C. A.; Johns E. M. C.; Macdonald A.; Shilling H.; Burgess R.; Weckhuysen D.; Bahlo M.; O'Brien T. J.; Todaro M.; Stamberger H.; Andrade D. M.; Sadoway T. R.; Mo K.; Krestel H.; Gallati S.; Papacostas S. S.; Kousiappa I.; Tanteles G. A.; Sterbova K.; Vlckova M.; Sedlackova L.; Lassuthova P.; Klein K. M.; Rosenow F.; Reif P. S.; Knake S.; Kunz W. S.; Zsurka G.; Elger C. E.; Bauer J.; Rademacher M.; Pendziwiat M.; Muhle H.; Rademacher A.; Van Baalen A.; Von Spiczak S.; Stephani U.; Afawi Z.; Korczyn A. D.; Kanaan M.; Canavati C.; Kurlemann G.; Muller-Schluter K.; Kluger G.; Hausler M.; Blatt I.; Lemke J. R.; Krey I.; Weber Y. G.; Wolking S.; Becker F.; Hengsbach C.; Rau S.; Maisch A. F.; Steinhoff B. J.; Schulze-Bonhage A.; Schubert-Bast S.; Schreiber H.; Borggrafe I.; Schankin C. J.; Mayer T.; Korinthenberg R.; Brockmann K.; Dennig D.; Madeleyn R.; Kalviainen R.; Auvinen P.; Saarela A.; Linnankivi T.; Lehesjoki A. -E.; Rees M. I.; Chung S. -K.; Pickrell W. O.; Powell R.; Schneider N.; Balestrini S.; Zagaglia S.; Braatz V.; Johnson M. R.; Auce P.; Sills G. J.; Baum L. W.; Sham P. C.; Cherny S. S.; Lui C. H. T.; Barisic N.; Delanty N.; Doherty C. P.; Shukralla A.; McCormack M.; El-Naggar H.; Canafoglia L.; Franceschetti S.; Castellotti B.; Granata T.; Zara F.; Iacomino M.; Madia F.; Vari M. S.; Mancardi M. M.; Vincenzo Salpietro; Bisulli F.; Tinuper P.; Licchetta L.; Pippucci T.; Stipa C.; Muccioli L.; Minardi R.; Gambardella A.; Labate A.; Annesi G.; Manna L.; Gagliardi M.; Parrini E.; Mei D.; Vetro A.; Bianchini C.; Montomoli M.; Doccini V.; Marini C.; Suzuki T.; Inoue Y.; Yamakawa K.; Birute T.; Ruta M.; Algirdas U.; Ruta P.; Jurgita G.; Ruta S.; Sadleir L. G.; King C.; Mountier E.; Caglayan S. H.; Arslan M.; Yapici Z.; Yis U.; Topaloglu P.; Kara B.; Turkdogan D.; Gundogdu-Eken A.; Bebek N.; Ugur-Iseri S.; Baykan B.; Salman B.; Haryanyan G.; Yucesan E.; Kesim Y.; Ozkara C.; Sheidley B. R.; Shain C.; Poduri A.; Buono R. J.; Ferraro T. N.; Sperling M. R.; Lo W.; Privitera M.; French J. A.; Schachter S.; Kuzniecky R. I.; Devinsky O.; Hegde M.; Khankhanian P.; Helbig K. L.; Ellis C. A.; Spalletta G.; Piras F.; Gili T.; Ciullo V. |
| Contributors: | Leu, C.; Stevelink, R.; Smith, A. W.; Goleva, S. B.; Kanai, M.; Ferguson, L.; Campbell, C.; Kamatani, Y.; Okada, Y.; Sisodiya, S. M.; Cavalleri, G. L.; Koeleman, B. P. C.; Lerche, H.; Jehi, L.; Davis, L. K.; Najm, I. M.; Palotie, A.; Daly, M. J.; Busch, R. M.; Lal, D.; Feng, Y. -C. A.; Howrigan, D. P.; Abbott, L. E.; Tashman, K.; Cerrato, F.; Churchhouse, C.; Gupta, N.; Neale, B. M.; Berkovic, S. F.; Goldstein, D. B.; Lowenstein, D. H.; Cossette, P.; Cotsapas, C.; De Jonghe, P.; Dixon-Salazar, T.; Guerrini, R.; Hakonarson, H.; Heinzen, E. L.; Helbig, I.; Kwan, P.; Marson, A. G.; Petrovski, S.; Kamalakaran, S.; Stewart, R.; Weckhuysen, S.; Depondt, C.; Dlugos, D. J.; Scheffer, I. E.; Striano, P.; Freyer, C.; Krause, R.; May, P.; Mckenna, K.; Regan, B. M.; Bellows, S. T.; Bennett, C. A.; Johns, E. M. C.; Macdonald, A.; Shilling, H.; Burgess, R.; Weckhuysen, D.; Bahlo, M.; O'Brien, T. J.; Todaro, M.; Stamberger, H.; Andrade, D. M.; Sadoway, T. R.; Mo, K.; Krestel, H.; Gallati, S.; Papacostas, S. S.; Kousiappa, I.; Tanteles, G. A.; Sterbova, K.; Vlckova, M.; Sedlackova, L.; Lassuthova, P.; Klein, K. M.; Rosenow, F.; Reif, P. S.; Knake, S.; Kunz, W. S.; Zsurka, G.; Elger, C. E.; Bauer, J.; Rademacher, M.; Pendziwiat, M.; Muhle, H.; Rademacher, A.; Van Baalen, A.; Von Spiczak, S.; Stephani, U.; Afawi, Z.; Korczyn, A. D.; Kanaan, M.; Canavati, C.; Kurlemann, G.; Muller-Schluter, K.; Kluger, G.; Hausler, M. |
| Publisher Information: | OXFORD; Oxford University Press |
| Publication Year: | 2019 |
| Collection: | Università degli Studi di Genova: CINECA IRIS |
| Subject Terms: | Common variant risk; Epilepsy; Genetic generalized epilepsy; Genetic; Cohort Studie; Cost of Illne; Databases; Factual; Epilepsies; Partial; Generalized; European Continental Ancestry Group; Female; Genetic Predisposition to Disease; Genetic Variation; Genome-Wide Association Study; Human; Male; Multifactorial Inheritance; Polymorphism; Single Nucleotide |
| Description: | Rare genetic variants can cause epilepsy, and genetic testing has been widely adopted for severe, paediatric-onset epilepsies. The phenotypic consequences of common genetic risk burden for epilepsies and their potential future clinical applications have not yet been determined. Using polygenic risk scores (PRS) from a European-ancestry genome-wide association study in generalized and focal epilepsy, we quantified common genetic burden in patients with generalized epilepsy (GE-PRS) or focal epilepsy (FE-PRS) from two independent non-Finnish European cohorts (Epi25 Consortium, n = 5705; Cleveland Clinic Epilepsy Center, n = 620; both compared to 20 435 controls). One Finnish-ancestry population isolate (Finnish-ancestry Epi25, n = 449; compared to 1559 controls), two European-ancestry biobanks (UK Biobank, n = 383 656; Vanderbilt biorepository, n = 49 494), and one Japaneseancestry biobank (BioBank Japan, n = 168 680) were used for additional replications. Across 8386 patients with epilepsy and 622 212 population controls, we found and replicated significantly higher GE-PRS in patients with generalized epilepsy of European-ancestry compared to patients with focal epilepsy (Epi25: P = 1.64×10-15; Cleveland: P = 2.85×10-4; Finnish-ancestry Epi25: P = 1.80×10-4) or population controls (Epi25: P = 2.35×10-70; Cleveland: P = 1.43×10-7; Finnish-ancestry Epi25: P = 3.11×10-4; UK Biobank and Vanderbilt biorepository meta-analysis: P = 7.99×10-4). FE-PRS were significantly higher in patients with focal epilepsy compared to controls in the non-Finnish, non-biobank cohorts (Epi25: P = 5.74×10-19; Cleveland: P = 1.69×10-6). European ancestry-derived PRS did not predict generalized epilepsy or focal epilepsy in Japanese-ancestry individuals. Finally, we observed a significant 4.6-fold and a 4.5-fold enrichment of patients with generalized epilepsy compared to controls in the top 0.5% highest GE-PRS of the two non-Finnish European cohorts (Epi25: P = 2.60×10-15; Cleveland: P = 1.39×10-2). We conclude that common variant risk ... |
| Document Type: | article in journal/newspaper |
| File Description: | STAMPA |
| Language: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/31608925; info:eu-repo/semantics/altIdentifier/wos/WOS:000504323200026; volume:142; firstpage:3473; lastpage:3481; numberofpages:9; journal:BRAIN; https://hdl.handle.net/11567/1028583 |
| DOI: | 10.1093/brain/awz292 |
| Availability: | https://hdl.handle.net/11567/1028583; https://doi.org/10.1093/brain/awz292 |
| Rights: | info:eu-repo/semantics/openAccess |
| Accession Number: | edsbas.1C071A57 |
| Database: | BASE |