Genome-wide identification and phenotypic characterization of seizure-associated copy number variations in 741,075 individuals.
Genome-wide identification and phenotypic characterization of seizure-associated copy number variations in 741,075 individuals.
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741,075 名个体中与癫痫发作相关的拷贝数变异的全基因组鉴定和表型特征。
DOI：
10.1038/s41467-023-39539-6
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发表时间：
2023-07-20
影响因子：
16.6
通讯作者：
Taneja, Randip S.
中科院分区：
文献类型：
--
作者：
Montanucci, Ludovica;Lewis-Smith, David;Collins, Ryan L.;Niestroj, Lisa-Marie;Parthasarathy, Shridhar;Xian, Julie;Ganesan, Shiva;Macnee, Marie;Bruenger, Tobias;Thomas, Rhys H.;Talkowski, Michael;Helbig, Ingo;Leu, Costin;Lal, Dennis;Motelow, Joshua E.;Povysil, Gundula;Dhindsa, Ryan S.;Stanley, Kate E.;Allen, Andrew S.;Goldstein, David B.;Feng, Yen-Chen Anne;Howrigan, Daniel P.;Abbott, Liam E.;Tashman, Katherine;Cerrato, Felecia;Cusick, Caroline;Singh, Tarjinder;Heyne, Henrike;Byrnes, Andrea E.;Churchhouse, Claire;Watts, Nick;Solomonson, Matthew;Lal, Dennis;Gupta, Namrata;Neale, Benjamin M.;Berkovic, Samuel F.;Lerche, Holger;Goldstein, David B.;Lowenstein, Daniel H.;Berkovic, Samuel F.;Lerche, Holger;Goldstein, David B.;Lowenstein, Daniel H.;Cavalleri, Gianpiero L.;Cossette, Patrick;Cotsapas, Chris;De Jonghe, Peter;Dixon-Salazar, Tracy;Guerrini, Renzo;Hakonarson, Hakon;Heinzen, Erin L.;Dhindsa, Ryan S.;Stanley, Kate E.;Helbig, Ingo;Kwan, Patrick;Marson, Anthony G.;Petrovski, Slave;Kamalakaran, Sitharthan;Sisodiya, Sanjay M.;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.;Bennett, Caitlin A.;Leech, Stephanie L.;Leu, Costin;Lewis-Smith, David;Berkovic, Samuel F.;Scheffer, Ingrid E.;Regan, Brigid M.;Bennett, Caitlin A.;Leech, Stephanie L.;O'Brien, Terence J.;Petrovski, Slave;Todaro, Marian;Kwan, Patrick;Weckhuysen, Sarah;De Jonghe, Peter;Stamberger, Hannah;Depondti, Chantal;Andrade, Danielle M.;Ali, Quratulain Zulfiqar;Sadoway, Tara R.;Krestel, Heinz;Schaller, Andre;Papacostas, Savvas S.;Kousiappa, Ioanna;Tanteles, George A.;Yiolanda, Christou;Sterbova, Katalin;Vlckova, Marketa;Sedlackova, Lucie;Lassuthova, Petra;Klein, Karl Martin;Rosenow, Felix;Reif, Philipp S.;Knake, Susanne;Neubauer, Bernd A.;Zimprich, Friedrich;Feucht, Martha;Reinthaler, Eva;Kunz, Wolfram S.;Zsurka, Gabor;Surges, Rainer;Baumgartner, Tobias H.;von Wrede, Randi;Helbig, Ingo;Klein, Karl Martin;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;Mueller-Schlueter, Karen;Kluger, Gerhard;Haeusler, Martin;Blatt, Ilan;Lemke, Johannes R.;Krey, Ilona;Lerche, Holger;Weber, Yvonne G.;Wolking, Stefan;Becker, Felicitas;Lauxmann, Stephan;Bosselmann, Christian;Kegele, Josua;Hengsbach, Christian;Rau, Sarah;Steinhoff, Bernhard J.;Schulze-Bonhage, Andreas;Borggrafe, Ingo;Schankin, Christoph J.;Schubert-Bast, Susanne;Schreiber, Herbert;Mayer, Thomas;Korinthenberg, Rudolf;Brockmann, Knut;Wolff, Markus;Kurlemann, Gerhard;Dennig, Dieter;Madeleyn, Rene;Kegele, Josua;Kalviainen, Reetta;Saarela, Anni;Timonen, Oskari;Linnankivi, Tarja;Lehesjoki, Anna-Elina;Rheims, Sylvain;Lesca, Gaetan;Ryvlin, Philippe;Maillard, Louis;Valton, Luc;Derambure, Philippe;Bartolomei, Fabrice;Hirsch, Edouard;Michel, Veronique;Chassoux, Francine;Rees, Mark I.;Chung, Seo-Kyung;Pickrell, William O.;Powell, Robert H. W.;Baker, Mark D.;Fonferko-Shadrach, Beata;Lawthom, Charlotte;Anderson, Joe;Sisodiya, Sanjay M.;Schneider, Natascha;Balestrini, Simona;Zagaglia, Sara;Braatz, Vera;Marson, Anthony G.;Johnson, Michael R.;Auce, Pauls;Sills, Graeme J.;Kwan, Patrick;Baum, Larry W.;Sham, Pakc.;Cherny, Stacey S.;Lui, Colin H. T.;Cavalleri, Gianpiero L.;Delanty, Norman;Doherty, Colin P.;Shukralla, Arif;El-Naggar, Hany;Widdess-Walsh, Peter;Barisic, Nina;Canafoglia, Laura;Franceschetti, Silvana;Castellotti, Barbara;Granata, Tiziana;Ragona, Francesca;Striano, Pasquale;Zara, Federico;Iacomino, Michele;Riva, Antonella;Madia, Francesca;Vari, Maria Stella;Salpietro, Vincenzo;Scala, Marcello;Mancardi, Maria Margherita;Lino, Nobili;Amadori, Elisa;Giacomini, Thea;Bisulli, Francesca;Pippucci, Tommaso;Licchetta, Laura;Minardi, Raffaella;Tinuper, Paolo;Muccioli, Lorenzo;Mostacci, Barbara;Gambardella, Antonio;Labate, Angelo;Annesi, Grazia;Manna, Lorella;Gagliardi, Monica;Guerrini, Renzo;Parrini, Elena;Mei, Davide;Vetro, Annalisa;Bianchini, Claudia;Montomoli, Martino;Doccini, Viola;Barba, Carmen;Hirose, Shinichi;Ishii, Atsushi;Suzuki, Toshimitsu;Inoue, Yushi;Yamakawa, Kazuhiro;Beydoun, Ahmad;Nasreddine, Wassim;Khoueiry-Zgheib, Nathalie;Tumiene, Birute;Utkus, Algirdas;Sadleir, Lynette G.;King, Chontelle;Caglayan, S. Hande;Arslan, Mutluay;Yapici, Zuhal;Topaloglu, Pinar;Kara, Bulent;Yis, Uluc;Turkdogan, Dilsad;Gundogdu-Eken, Asli;Bebek, Nerses;Ugur-Iseri, Sibel;Baykan, Betul;Salman, Baris;Haryanyan, Garen;Yucesan, Emrah;Kesim, Yesim;Ozkara, Cigdem;Tsai, Meng-Han;Ho, Chen-Jui;Lin, Chih-Hsiang;Lin, Kuang-Lin;Chou, I-Jun;Poduri, Annapurna;Shiedley, Beth R.;Shain, Catherine;Noebels, Jeffrey L.;Goldman, Alicia;Busch, Robyn M.;Jehi, Lara;Najm, Imad M.;Lal, Dennis;Ferguson, Lisa;Khoury, Jean;Glauser, Tracy A.;Clark, Peggy O.;Buono, Russell J.;Ferraro, Thomas N.;Sperling, Michael R.;Dlugos, Dennis J.;Lo, Warren;Privitera, Michael;French, Jacqueline A.;Cossette, Patrick;Schachter, Steven;Hakonarson, Hakon;Lowenstein, Daniel H.;Kuzniecky, Ruben I.;Dlugos, Dennis J.;Devinsky, Orrin;Lowenstein, Daniel H.;Kuzniecky, Ruben I.;French, Jacqueline A.;Hegde, Manu;Greenberg, David A.;Helbig, Ingo;Ellis, Colin A.;Goldberg, Ethan;Helbig, Katherine L.;Lewis-Smith, David;Cosico, Mahgenn;Vaidiswaran, Priya;Fitch, Eryn;Newton, Charles R. J. C.;Kariuki, SymonM.;Wagner, Ryan G.;Owusu-Agyei, Seth;Cole, Andrew J.;McGraw, ChristopherM.;Siena, S. Anthony;Davis, Lea;Hucks, Donald;Faucon, Annika;Wu, David;Abou-Khalil, Bassel W.;Haas, Kevin;Taneja, Randip S.
Copy number variants (CNV) are established risk factors for neurodevelopmental disorders with seizures or epilepsy. With the hypothesis that seizure disorders share genetic risk factors, we pooled CNV data from 10,590 individuals with seizure disorders, 16,109 individuals with clinically validated epilepsy, and 492,324 population controls and identified 25 genome-wide significant loci, 22 of which are novel for seizure disorders, such as deletions at 1p36.33, 1q44, 2p21-p16.3, 3q29, 8p23.3-p23.2, 9p24.3, 10q26.3, 15q11.2, 15q12-q13.1, 16p12.2, 17q21.31, duplications at 2q13, 9q34.3, 16p13.3, 17q12, 19p13.3, 20q13.33, and reciprocal CNVs at 16p11.2, and 22q11.21. Using genetic data from additional 248,751 individuals with 23 neuropsychiatric phenotypes, we explored the pleiotropy of these 25 loci. Finally, in a subset of individuals with epilepsy and detailed clinical data available, we performed phenome-wide association analyses between individual CNVs and clinical annotations categorized through the Human Phenotype Ontology (HPO). For six CNVs, we identified 19 significant associations with specific HPO terms and generated, for all CNVs, phenotype signatures across 17 clinical categories relevant for epileptologists. This is the most comprehensive investigation of CNVs in epilepsy and related seizure disorders, with potential implications for clinical practice. Here, the authors perform a meta-analysis in 26,699 people with seizures and 492,324 controls to identify 25 genome-wide significant copy-number variants. The discovered loci point to known disease genes and associations with clinical annotations.
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影响因子：
10.6
作者：
Amiet, Claire;Gourfinkel-An, Isabelle;Cohen, David
通讯作者：
Cohen, David
影响因子：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ
影响因子：
3.5
作者：
Dibbens, Leanne M.;Mullen, Saul;Berkovic, Samuel F.
通讯作者：
Berkovic, Samuel F.
影响因子：
3.1
作者：
Chen, Dong-Hui;Latimer, Caitlin;Bird, Thomas D.
通讯作者：
Bird, Thomas D.
影响因子：
7.7
作者：
Borodulin, Katja;Tolonen, Hanna;Vartiainen, Erkki
通讯作者：
Vartiainen, Erkki