Polygenic burden in focal and generalized epilepsies
| Autor: | 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., Salpietro V., 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. |
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| Přispěvatelé: | 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., Salpietro V., 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., Commission of the European Communities, Medical Research Council (MRC), Tumienė, Birutė, Mameniškienė, Rūta, Utkus, Algirdas, Praninskienė, Rūta, Grikinienė, Jurgita, Samaitienė-Aleknienė, Rūta, Centre of Excellence in Complex Disease Genetics, Aarno Palotie / Principal Investigator, Institute for Molecular Medicine Finland, Genomics of Neurological and Neuropsychiatric Disorders, University of Helsinki, Helsinki Institute of Life Science HiLIFE, Department of Medical and Clinical Genetics |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Multifactorial Inheritance Epi25 Consortium Databases Factual FEATURES Genome-wide association study Epilepsies 3124 Neurology and psychiatry Cohort Studies Epilepsy 0302 clinical medicine Cost of Illness 1ST SEIZURE HISTORY genetics POPULATION 11 Medical and Health Sciences education.field_of_study medicine.diagnostic_test SCORES Single Nucleotide Biobank 3. Good health 17 Psychology and Cognitive Sciences Genetic generalized epilepsy Epilepsy Generalized Female Partial Cohort study Human medicine.medical_specialty Population European Continental Ancestry Group Clinical Neurology BIOBANK Polymorphism Single Nucleotide epilepsy genetic generalized epilepsy common variant risk Databases 03 medical and health sciences Genetic Internal medicine medicine Journal Article Genetics Humans Genetic Predisposition to Disease Polymorphism GENOME-WIDE ASSOCIATION Generalized epilepsy education SEIZURE RECURRENCE Factual METAANALYSIS Genetic testing Neurology & Neurosurgery RISK PREDICTION Generalized business.industry 3112 Neurosciences Common variant risk Genetic Variation Original Articles medicine.disease Comorbidity Cost of Illne Epilepsies Partial Genome-Wide Association Study 030104 developmental biology Neurology (clinical) Cohort Studie business 030217 neurology & neurosurgery |
| Zdroj: | Brain 142 (2019): 3473–3481. doi:10.1093/brain/awz292 info:cnr-pdr/source/autori:Leu, Costin; Stevelink, Remi; Smith, Alexander W.; Goleva, Slavina B.; Kanai, Masahiro; Ferguson, Lisa; Campbell, Ciaran; Kamatani, Yoichiro; Okada, Yukinori; Sisodiya, Sanjay M.; Cavalleri, Gianpiero L.; Koeleman, Bobby P.C.; Lerche, Holger; Jehi, Lara; Davis, Lea K.; Najm, Imad M.; Palotie, Aarno; Daly, Mark J.; Busch, Robyn M.; Lal, Dennis; Feng, Yen Chen Anne; Howrigan, Daniel P.; Abbott, Liam E.; Tashman, Katherine; Cerrato, Felecia; Churchhouse, Claire; Gupta, Namrata; Neale, Benjamin M.; Berkovic, Samuel F.; Goldstein, David B.; Lowenstein, Daniel H.; Cossette, Patrick; Cotsapas, Chris; De Jonghe, Peter; Dixon-Salazar, Tracy; Guerrini, Renzo; Hakonarson, Hakon; Heinzen, Erin L.; Helbig, Ingo; Kwan, Patrick; Marson, Anthony G.; Petrovski, Slavé; Kamalakaran, Sitharthan; Stewart, Randy; Weckhuysen, Sarah; Depondt, Chantal; Dlugos, Dennis J.; Scheffer, Ingrid E.; Striano, Pasquale; Freyer, Catharine; Krause, Roland; May, Patrick; McKenna, Kevin; Regan, Brigid M.; Bellows, Susannah T.; Bennett, Caitlin A.; Johns, Esther M.C.; Macdonald, Alexandra; Shilling, Hannah; Burgess, Rosemary; Weckhuysen, Dorien; Bahlo, Melanie; O'Brien, Terence J.; Todaro, Marian; Stamberger, Hannah; Andrade, Danielle M.; Sadoway, Tara R.; Mo, Kelly; Krestel, Heinz; Gallati, Sabina; Papacostas, Savvas S.; Kousiappa, Ioanna; Tanteles, George A.; ?terbová, Katalin; Vlcková, Markéta; Sedlácková, Lucie; La??uthová, Petra; Klein, Karl Martin; Rosenow, Felix; Reif, Philipp S.; Knake, Susanne; Kunz, Wolfram S.; Zsurka, Gábor; Elger, Christian E.; Bauer, Jürgen; Rademacher, Michael; Pendziwiat, Manuela; Muhle, Hiltrud; Rademacher, Annika; Van Baalen, Andreas; Von Spiczak, Sarah; Stephani, Ulrich; Afawi, Zaid; Korczyn, Amos D.; Kanaan, Moien; Canavati, Christina; Kurlemann, Gerhard; Müller-Schlüter, Karen; Kluger, Gerhard; Häusler, Martin/titolo:Polygenic burden in focal and generalized epilepsies/doi:10.1093%2Fbrain%2Fawz292/rivista:Brain (Print)/anno:2019/pagina_da:3473/pagina_a:3481/intervallo_pagine:3473–3481/volume:142 Brain, Oxford : Oxford university press, 2019, vol. 142, no. 11, p. 3473-3481 Brain : a journal of neurology, 142(11), 3473. Oxford University Press |
| ISSN: | 0006-8950 |
| DOI: | 10.1093/brain/awz292 |
| Popis: | See Hansen and Møller (doi:10.1093/brain/awz318) for a scientific commentary on this article. Using polygenic risk scores from a genome-wide association study in generalized and focal epilepsy, Leu et al. reveal a significantly higher genetic burden for epilepsy in multiple cohorts of people with epilepsy compared to population controls. Quantification of common variant burden may be valuable for epilepsy prognosis and treatment. 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 Japanese-ancestry 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 associated with epilepsy is significantly enriched in multiple cohorts of patients with epilepsy compared to controls—in particular for generalized epilepsy. As sample sizes and PRS accuracy continue to increase with further common variant discovery, PRS could complement established clinical biomarkers and augment genetic testing for patient classification, comorbidity research, and potentially targeted treatment. |
| Databáze: | OpenAIRE |
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