The Genetic Makeup of the Electrocardiogram.
The Genetic Makeup of the Electrocardiogram.
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DOI：
10.1016/j.cels.2020.08.005
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发表时间：
2020-09-23
期刊：
影响因子：
9.3
通讯作者：
van der Harst P
中科院分区：
文献类型：
--
作者：
Verweij N;Benjamins JW;Morley MP;van de Vegte YJ;Teumer A;Trenkwalder T;Reinhard W;Cappola TP;van der Harst P
The electrocardiogram (ECG) is one of the most useful non-invasive diagnostic tests for a wide array of cardiac disorders. Traditional approaches to analyzing ECGs focus on individual segments. Here, we performed comprehensive deep phenotyping of 77,190 ECGs in the UK Biobank across the complete cycle of cardiac conduction, resulting in 500 spatial-temporal datapoints, across 10 million genetic variants. In addition to characterizing polygenic risk scores for the traditional ECG segments, we identified over 300 genetic loci that are statistically associated with the high-dimensional representation of the ECG. We established the genetic ECG signature for dilated cardiomyopathy, associated the BAG3, HSPB7/CLCNKA, PRKCA, TMEM43, and OBSCN loci with disease risk and confirmed this association in an independent cohort. In total, our work demonstrates that a high-dimensional analysis of the entire ECG provides unique opportunities for studying cardiac biology and disease and furthering drug development. Verweij et al. performed high-dimensional phenotyping of the electrocardiogram followed by a large-scale genome-wide association study. The authors show that genetic variants have unique electrocardiographic signatures and that particular signatures relate to dilated cardiomyopathy and early repolarization, implicating genetic loci including BAG3, TMEM43, PRKCA, OBSCN, DKK1, and KCDN3.
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影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
影响因子：
30.8
作者：
Arking, Dan E.;Pulit, Sara L.;Crotti, Lia;Van der Harst, Pim;Munroe, Patricia B.;Koopmann, Tamara T.;Sotoodehnia, Nona;Rossin, Elizabeth J.;Morley, Michael;Wang, Xinchen;Johnson, Andrew D.;Lundby, Alicia;Gudbjartsson, Daniel F.;Noseworthy, Peter A.;Eijgelsheim, Mark;Bradford, Yuki;Tarasov, Kirill V.;Dorr, Marcus;Miiller-Nurasyid, Martina;Lahtinen, Annukka M.;Nolte, Ilja M.;Smith, Albert Vernon;Bis, Joshua C.;Isaacs, Aaron;Newhouse, Stephen J.;Evans, Daniel S.;Post, Wendy S.;Waggott, Daryl;Lyytikainen, Leo-Pekka;Hicks, Andrew A.;Eisele, Lewin;Ellinghaus, David;Hayward, Caroline;Navarro, Pau;Ulivi, Sheila;Tanaka, Toshiko;Tester, David J.;Chatel, Stephanie;Gustafsson, Stefan;Kumari, Meena;Morris, Richard W.;Naluai, Asa T.;Padmanabhan, Sandosh;Kluttig, Alexander;Strohmer, Bernhard;Panayiotou, Andrie G.;Torres, Maria;Knoflach, Michael;Hubacek, Jaroslav A.;Slowikowski, Kamil;Raychaudhuri, Soumya;Kumar, Runjun D.;Harris, Tamara B.;Launer, Lenore J.;Shuldiner, Alan R.;Alonso, Alvaro;Bader, Joel S.;EhreT, Georg;Huang, Hailiang;Kao, W. H. Linda;Strait, James B.;Macfarlane, Peter W.;Brown, Morris;Caulfield, Mark J.;Samani, Nilesh J.;Kronenberg, Florian;Willeit, Johann;Smith, J. Gustav;Greiser, Karin H.;Schwabedissen, Henriette Meyer Zu;Werdan, Karl;Carella, Massimo;Zelante, Leopoldo;Heckbert, Susan R.;Psaty, Bruce M.;Rotter, Jerome I.;Kolcic, Ivana;Poagek, Ozren;Wright, Alan F.;Griffin, Maura;Daly, Mark J.;Arnar, David O.;Holm, Hilma;Thorsteinsdottir, Unnur;Denny, Joshua C.;Roden, Dan M.;Zuvich, Rebecca L.;Emilsson, Valur;Plump, Andrew S.;Larson, Martin G.;O'Donnell, Christopher J.;Yin, Xiaoyan;Bobboll, Marco;D'Adamo, Adamo P.;Iorio, Annamaria;Sinagra, Gianfranco;Carracedo, Angel;Cummings, Steven R.;Nalls, Michael A.;Jula, Antti;Kontula, Kimmo K.;Marjamaa, Annukka;Oikarinen, Lasse;Perola, Markus;Porthan, Kimmo;Erbe, Raimund;Hoffmann, Per;Jockel, Karl-Heinz;Kalsch, Hagen;Nothen, Markus M.;Den Hoed, Marcel;Loos, Ruth J. F.;Thelle, Dag S.;Gieger, Christian;Meitinger, Thomas;Perz, Siegfried;Peters, Annette;Pruchal, Hanna;Sinner, Moritz F.;Waldenberger, Melanie;De Boer, Rudolf A.;Franke, Lude;Van der Vleuten, Pieter A.;Beckmann, Britt Maria;Martens, Eimo;Bardail, Abdennasser;Hofman, Nynke;Wilde, Arthur A. M.;Behr, Elijah R.;Dalageorgou, Chrysoula;Giudicessi, John R.;Medeiros-Domingo, Argelia;Barc, Julien;Kyndt, Florence;Probst, Vincent;Ghidoni, Alice;Insolia, Roberto;Hamilton, Robert M.;Scherer, Stephen W.;Brandimarto, Jeffrey;Margulies, Kenneth;Moravec, Christine E.;Del Greco, Fabiola;Fuchsberger, Christian;O'Connell, Jeffrey R.;Lee, Wai K.;Watt, Graham C. M.;Campbell, Harry;Wild, Sarah H.;El Mokhtari, Nour E.;Frey, Norbert;Asselbergs, Folkert W.;Leach, Irene Mateo;Navis, Gerjan;Van den Berg, Maarten P.;Van Veldhuisen, Dirk J.;Kellis, Manolis;Krijthe, Bouwe P.;Franco, Oscar H.;Hofman, Albert;Kors, Jan A.;Uitterlinden, Andre G.;Witteman, Jacqueline C. M.;Kedenko, Lyudmyla;Lamina, Claudia;Oostra, Ben A.;Abecasis, Goncalo R.;Lakatta, Edward G.;Mulas, Antonella;Orru, Marco;Schlessinger, David;Uda, Manuela;Markus, Marcello R. P.;Volker, Uwe;Snieder, Harold;Spector, Timothy D.;Arnlov, Johan;Lind, Lars;Sundstrom, Johan;Syvanen, Ann-Christine;Kivimaki, Mika;Kahonen, Mika;Mononen, Nina;Raitakari, I. T.;Viikari, Jorma S.;Adamkova, Vera;Kiech, Stefan;Brion, Maria;Nicolaides, Andrew N.;Paulweber, Bernhard;Haerting, Johannes;Dominiczak, Anna F.;Nyberg, Fredrik;Whincup, Peter H.;Hingorani, Aroon D.;Schott, Jean-Jacques;Bezzina, Connie R.;Ingelsson, Erik;Ferrucci, Luigi;Gaspariniin, Paolo;Wilson, James F.;Rudan, Igor;Franke, Andre;Miihleisen, Thomas W.;Pramstaller, Peter P.;Lehtimaki, Terho J.;Paterson, Andrew D.;Parsa, Afshin;Liu, Yongmei;Van Duijn, Cornelia M.;Siscovick, David S.;Gudnason, Vilmundur;Jamshidi, Yalda;Salomaa, Veikko;Felix, Stephan B.;Sanna, Serena;Ritchie, Marylyn D.;Stricker, Bruno H.;Stefansson, Karl;Boyer, Laurie A.;Cappola, Thomas P.;Olsen, Jesper V.;Lage, Kasper;Schwartz, Peter J.;Kaab, Stefan;Chakravarti, Aravinda;Ackerman, Michael J.;Pfeufer, Arne;De Bakker, Paul I. W.;Newton-Cheh, Christopher
通讯作者：
Newton-Cheh, Christopher
影响因子：
--
作者：
Marston S
通讯作者：
Marston S
影响因子：
30.8
作者：
Nielsen JB;Thorolfsdottir RB;Fritsche LG;Zhou W;Skov MW;Graham SE;Herron TJ;McCarthy S;Schmidt EM;Sveinbjornsson G;Surakka I;Mathis MR;Yamazaki M;Crawford RD;Gabrielsen ME;Skogholt AH;Holmen OL;Lin M;Wolford BN;Dey R;Dalen H;Sulem P;Chung JH;Backman JD;Arnar DO;Thorsteinsdottir U;Baras A;O'Dushlaine C;Holst AG;Wen X;Hornsby W;Dewey FE;Boehnke M;Kheterpal S;Mukherjee B;Lee S;Kang HM;Holm H;Kitzman J;Shavit JA;Jalife J;Brummett CM;Teslovich TM;Carey DJ;Gudbjartsson DF;Stefansson K;Abecasis GR;Hveem K;Willer CJ
通讯作者：
Willer CJ
影响因子：
30.8
作者：
Loh, Po-Ru;Tucker, George;Bulik-Sullivan, Brendan K.;Vilhjalmsson, Bjarni J.;Finucane, Hilary K.;Salem, Rany M.;Chasman, Daniel I.;Ridker, Paul M.;Neale, Benjamin M.;Berger, Bonnie;Patterson, Nick;Price, Alkes L.
通讯作者：
Price, Alkes L.