Abou-Khalil, Bassel, Auce, Pauls, Avbersek, Andreja, Bahlo, Melanie ORCID: 0000-0001-5132-0774, Balding, David J., Bast, Thomas, Baum, Larry, Becker, Albert J., Becker, Felicitas, Berghuis, Bianca, Berkovic, Samuel F., Boysen, Katja E., Bradfield, Jonathan P., Brody, Lawrence C., Buono, Russell J., Campbell, Ellen, Cascino, Gregory D., Catarino, Claudia B., Cavalleri, Gianpiero L., Cherny, Stacey S., Chinthapalli, Krishna, Coffey, Alison J., Compston, Alastair, Coppola, Antonietta, Cossette, Patrick, Craig, John J., de Haan, Gerrit-Jan, De Jonghe, Peter, de Kovel, Carolien G. F., Delanty, Norman, Depondt, Chantal, Devinsky, Orrin ORCID: 0000-0003-0044-4632, Dlugos, Dennis J., Doherty, Colin P., Elger, Christian E., Eriksson, Johan G., Ferraro, Thomas N., Feucht, Martha, Francis, Ben, Franke, Andre, French, Jacqueline A., Freytag, Saskia, Gaus, Verena, Geller, Eric B., Gieger, Christian, Glauser, Tracy, Glynn, Simon, Goldstein, David B., Gui, Hongsheng ORCID: 0000-0002-0460-7446, Guo, Youling, Haas, Kevin F., Hakonarson, Hakon, Hallmann, Kerstin, Haut, Sheryl, Heinzen, Erin L., Helbig, Ingo, Hengsbach, Christian, Hjalgrim, Helle, Iacomino, Michele, Ingason, Andres, Jamnadas-Khoda, Jennifer ORCID: 0000-0002-3372-4924, Johnson, Michael R., Kalviainen, Reetta, Kantanen, Anne-Mari, Kasperaviciute, Dalia, Trenite, Dorothee Kasteleijn-Nolst, Kirsch, Heidi E., Knowlton, Robert C., Koeleman, Bobby P. C., Krause, Roland ORCID: 0000-0001-9938-7126, Krenn, Martin ORCID: 0000-0003-3026-3082, Kunz, Wolfram S., Kuzniecky, Ruben, Kwan, Patrick, Lal, Dennis, Lau, Yu-Lung, Lehesjoki, Anna-Elina, Lerche, Holger, Leu, Costin ORCID: 0000-0003-0598-3301, Lieb, Wolfgang, Lindhout, Dick, Lo, Warren D., Lopes-Cendes, Iscia ORCID: 0000-0002-6221-6822, Lowenstein, Daniel H., Malovini, Alberto, Marson, Anthony G., Mayer, Thomas, McCormack, Mark, Mills, James L., Mirza, Nasir, Moerzinger, Martina, Moller, Rikke S., Molloy, Anne M., Muhle, Hiltrud, Newton, Mark, Ng, Ping-Wing, Noethen, Markus M., Nuernberg, Peter, O'Brien, Terence J., Oliver, Karen L., Palotie, Aarno, Pangilinan, Faith, Peter, Sarah, Petrovski, Slave, Poduri, Annapurna, Privitera, Michael, Radtke, Rodney, Rau, Sarah, Reif, Philipp S., Reinthaler, Eva M., Rosenow, Felix, Sander, Josemir W., Sander, Thomas, Scattergood, Theresa, Schachter, Steven C., Schankin, Christoph J., Scheffer, Ingrid E., Schmitz, Bettina, Schoch, Susanne, Sham, Pak C., Shih, Jerry J., Sills, Graeme J., Sisodiya, Sanjay M., Slattery, Lisa, Smith, Alexander, Smith, David F., Smith, Michael C., Smith, Philip E., Sonsma, Anja C. M., Speed, Doug ORCID: 0000-0002-0096-9765, Sperling, Michael R., Steinhoff, Bernhard J., Stephani, Ulrich, Stevelink, Remi, Strauch, Konstantin, Striano, Pasquale ORCID: 0000-0002-6065-1476, Stroink, Hans, Surges, Rainer, Tan, K. Meng, Thio, Liu Lin ORCID: 0000-0002-9779-7903, Thomas, G. Neil, Todaro, Marian, Tozzi, Rossana, Vari, Maria S., Vining, Eileen P. G., Visscher, Frank, von Spiczak, Sarah, Walley, Nicole M., Weber, Yvonne G., Wei, Zhi ORCID: 0000-0001-6059-4267, Weisenberg, Judith, Whelan, Christopher D., Widdess-Walsh, Peter, Wolff, Markus ORCID: 0000-0001-5640-0888, Wolking, Stefan ORCID: 0000-0002-1460-6623, Yang, Wanling, Zara, Federico and Zimprich, Fritz ORCID: 0000-0002-6998-5480 (2018). Genome-wide mega-analysis identifies 16 loci and highlights diverse biological mechanisms in the common epilepsies. Nat. Commun., 9. LONDON: NATURE PUBLISHING GROUP. ISSN 2041-1723

Full text not available from this repository.

Abstract

The epilepsies affect around 65 million people worldwide and have a substantial missing heritability component. We report a genome-wide mega-analysis involving 15,212 individuals with epilepsy and 29,677 controls, which reveals 16 genome-wide significant loci, of which 11 are novel. Using various prioritization criteria, we pinpoint the 21 most likely epilepsy genes at these loci, with the majority in genetic generalized epilepsies. These genes have diverse biological functions, including coding for ion-channel subunits, transcription factors and a vitamin-B6 metabolism enzyme. Converging evidence shows that the common variants associated with epilepsy play a role in epigenetic regulation of gene expression in the brain. The results show an enrichment for monogenic epilepsy genes as well as known targets of antiepileptic drugs. Using SNP-based heritability analyses we disentangle both the unique and overlapping genetic basis to seven different epilepsy subtypes. Together, these findings provide leads for epilepsy therapies based on underlying pathophysiology.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Abou-Khalil, BasselUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Auce, PaulsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Avbersek, AndrejaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bahlo, MelanieUNSPECIFIEDorcid.org/0000-0001-5132-0774UNSPECIFIED
Balding, David J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bast, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baum, LarryUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Becker, Albert J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Becker, FelicitasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Berghuis, BiancaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Berkovic, Samuel F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boysen, Katja E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bradfield, Jonathan P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brody, Lawrence C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Buono, Russell J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Campbell, EllenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cascino, Gregory D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Catarino, Claudia B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cavalleri, Gianpiero L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cherny, Stacey S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chinthapalli, KrishnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Coffey, Alison J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Compston, AlastairUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Coppola, AntoniettaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cossette, PatrickUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Craig, John J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Haan, Gerrit-JanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
De Jonghe, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Kovel, Carolien G. F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Delanty, NormanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Depondt, ChantalUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Devinsky, OrrinUNSPECIFIEDorcid.org/0000-0003-0044-4632UNSPECIFIED
Dlugos, Dennis J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Doherty, Colin P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Elger, Christian E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eriksson, Johan G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ferraro, Thomas N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Feucht, MarthaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Francis, BenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Franke, AndreUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
French, Jacqueline A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Freytag, SaskiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gaus, VerenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Geller, Eric B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gieger, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Glauser, TracyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Glynn, SimonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Goldstein, David B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gui, HongshengUNSPECIFIEDorcid.org/0000-0002-0460-7446UNSPECIFIED
Guo, YoulingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haas, Kevin F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hakonarson, HakonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hallmann, KerstinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haut, SherylUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heinzen, Erin L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Helbig, IngoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hengsbach, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hjalgrim, HelleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Iacomino, MicheleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ingason, AndresUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jamnadas-Khoda, JenniferUNSPECIFIEDorcid.org/0000-0002-3372-4924UNSPECIFIED
Johnson, Michael R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kalviainen, ReettaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kantanen, Anne-MariUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kasperaviciute, DaliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Trenite, Dorothee Kasteleijn-NolstUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kirsch, Heidi E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Knowlton, Robert C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koeleman, Bobby P. C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krause, RolandUNSPECIFIEDorcid.org/0000-0001-9938-7126UNSPECIFIED
Krenn, MartinUNSPECIFIEDorcid.org/0000-0003-3026-3082UNSPECIFIED
Kunz, Wolfram S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kuzniecky, RubenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kwan, PatrickUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lal, DennisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lau, Yu-LungUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lehesjoki, Anna-ElinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lerche, HolgerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Leu, CostinUNSPECIFIEDorcid.org/0000-0003-0598-3301UNSPECIFIED
Lieb, WolfgangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lindhout, DickUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lo, Warren D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lopes-Cendes, IsciaUNSPECIFIEDorcid.org/0000-0002-6221-6822UNSPECIFIED
Lowenstein, Daniel H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Malovini, AlbertoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Marson, Anthony G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mayer, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
McCormack, MarkUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mills, James L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mirza, NasirUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moerzinger, MartinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moller, Rikke S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Molloy, Anne M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Muhle, HiltrudUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Newton, MarkUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ng, Ping-WingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Noethen, Markus M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nuernberg, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
O'Brien, Terence J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Oliver, Karen L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Palotie, AarnoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pangilinan, FaithUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peter, SarahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Petrovski, SlaveUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Poduri, AnnapurnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Privitera, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Radtke, RodneyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rau, SarahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reif, Philipp S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reinthaler, Eva M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rosenow, FelixUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sander, Josemir W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sander, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Scattergood, TheresaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schachter, Steven C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schankin, Christoph J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Scheffer, Ingrid E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmitz, BettinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schoch, SusanneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sham, Pak C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shih, Jerry J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sills, Graeme J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sisodiya, Sanjay M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Slattery, LisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Smith, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Smith, David F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Smith, Michael C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Smith, Philip E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sonsma, Anja C. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Speed, DougUNSPECIFIEDorcid.org/0000-0002-0096-9765UNSPECIFIED
Sperling, Michael R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Steinhoff, Bernhard J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stephani, UlrichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stevelink, RemiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Strauch, KonstantinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Striano, PasqualeUNSPECIFIEDorcid.org/0000-0002-6065-1476UNSPECIFIED
Stroink, HansUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Surges, RainerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tan, K. MengUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thio, Liu LinUNSPECIFIEDorcid.org/0000-0002-9779-7903UNSPECIFIED
Thomas, G. NeilUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Todaro, MarianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tozzi, RossanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vari, Maria S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vining, Eileen P. G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Visscher, FrankUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
von Spiczak, SarahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Walley, Nicole M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weber, Yvonne G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wei, ZhiUNSPECIFIEDorcid.org/0000-0001-6059-4267UNSPECIFIED
Weisenberg, JudithUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Whelan, Christopher D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Widdess-Walsh, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wolff, MarkusUNSPECIFIEDorcid.org/0000-0001-5640-0888UNSPECIFIED
Wolking, StefanUNSPECIFIEDorcid.org/0000-0002-1460-6623UNSPECIFIED
Yang, WanlingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zara, FedericoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zimprich, FritzUNSPECIFIEDorcid.org/0000-0002-6998-5480UNSPECIFIED
URN: urn:nbn:de:hbz:38-162261
DOI: 10.1038/s41467-018-07524-z
Journal or Publication Title: Nat. Commun.
Volume: 9
Date: 2018
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 2041-1723
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
LD SCORE REGRESSION; SUSCEPTIBILITY LOCI; GENETIC ARCHITECTURE; SNP HERITABILITY; ILAE COMMISSION; FRONTAL-LOBE; ASSOCIATION; METAANALYSIS; EXPRESSION; ABSENCEMultiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/16226

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