52 Genetic Loci Influencing Myocardial Mass

Research output: Contribution to journalJournal articlepeer-review

Standard

52 Genetic Loci Influencing Myocardial Mass. / van der Harst, Pim; van Setten, Jessica; Verweij, Niek; Vogler, Georg; Franke, Lude; Maurano, Matthew T; Wang, Xinchen; Mateo Leach, Irene; Eijgelsheim, Mark; Sotoodehnia, Nona; Hayward, Caroline; Sorice, Rossella; Meirelles, Osorio; Lyytikäinen, Leo-Pekka; Polašek, Ozren; Tanaka, Toshiko; Arking, Dan E; Ulivi, Sheila; Trompet, Stella; Müller-Nurasyid, Martina; Smith, Albert V; Dörr, Marcus; Kerr, Kathleen F; Magnani, Jared W; Del Greco M, Fabiola; Zhang, Weihua; Nolte, Ilja M; Silva, Claudia T; Padmanabhan, Sandosh; Tragante, Vinicius; Esko, Tõnu; Abecasis, Gonçalo R; Adriaens, Michiel E; Andersen, Karl; Barnett, Phil; Bis, Joshua C; Bodmer, Rolf; Buckley, Brendan M; Campbell, Harry; Cannon, Megan V; Chakravarti, Aravinda; Chen, Lin Y; Delitala, Alessandro; Devereux, Richard B; Doevendans, Pieter A; Dominiczak, Anna F; Ferrucci, Luigi; Ford, Ian; Gieger, Christian; Harris, Tamara B; Haugen, Eric; Heinig, Matthias; Hernandez, Dena G; Hillege, Hans L; Hirschhorn, Joel N; Hofman, Albert; Hubner, Norbert; Hwang, Shih-Jen; Iorio, Annamaria; Kähönen, Mika; Kellis, Manolis; Kolcic, Ivana; Kooner, Ishminder K; Kooner, Jaspal S; Kors, Jan A; Lakatta, Edward G; Lage, Kasper; Launer, Lenore J; Levy, Daniel; Lundby, Alicia; Macfarlane, Peter W; May, Dalit; Meitinger, Thomas; Metspalu, Andres; Nappo, Stefania; Naitza, Silvia; Neph, Shane; Nord, Alex S; Nutile, Teresa; Okin, Peter M; Olsen, Jesper V; Oostra, Ben A; Penninger, Josef M; Pennacchio, Len A; Pers, Tune H; Perz, Siegfried; Peters, Annette; Pinto, Yigal M; Pfeufer, Arne; Pilia, Maria Grazia; Pramstaller, Peter P; Prins, Bram P; Raitakari, Olli T; Raychaudhuri, Soumya; Rice, Ken M; Rossin, Elizabeth J; Rotter, Jerome I; Schafer, Sebastian; Schlessinger, David; Schmidt, Carsten O; Sehmi, Jobanpreet; Silljé, Herman H W; Sinagra, Gianfranco; Sinner, Moritz F; Slowikowski, Kamil; Soliman, Elsayed Z; Spector, Timothy D; Spiering, Wilko; Stamatoyannopoulos, John A; Stolk, Ronald P; Strauch, Konstantin; Tan, Sian-Tsung; Tarasov, Kirill V; Trinh, Bosco; Uitterlinden, Andre G; van den Boogaard, Malou; van Duijn, Cornelia M; van Gilst, Wiek H; Viikari, Jorma S; Visscher, Peter M; Vitart, Veronique; Völker, Uwe; Waldenberger, Melanie; Weichenberger, Christian X; Westra, Harm-Jan; Wijmenga, Cisca; Wolffenbuttel, Bruce H; Yang, Jian; Bezzina, Connie R; Munroe, Patricia B; Snieder, Harold; Wright, Alan F; Rudan, Igor; Boyer, Laurie A; Asselbergs, Folkert W; van Veldhuisen, Dirk J; Stricker, Bruno H; Psaty, Bruce M; Ciullo, Marina; Sanna, Serena; Lehtimäki, Terho; Wilson, James F; Bandinelli, Stefania; Alonso, Alvaro; Gasparini, Paolo; Jukema, J Wouter; Kääb, Stefan; Gudnason, Vilmundur; Felix, Stephan B; Heckbert, Susan R; de Boer, Rudolf A; Newton-Cheh, Christopher; Hicks, Andrew A; Chambers, John C; Jamshidi, Yalda; Visel, Axel; Christoffels, Vincent M; Isaacs, Aaron; Samani, Nilesh J; de Bakker, Paul I W.

In: Journal of the American College of Cardiology, Vol. 68, No. 13, 27.09.2016, p. 1435-48.

Research output: Contribution to journalJournal articlepeer-review

Harvard

van der Harst, P, van Setten, J, Verweij, N, Vogler, G, Franke, L, Maurano, MT, Wang, X, Mateo Leach, I, Eijgelsheim, M, Sotoodehnia, N, Hayward, C, Sorice, R, Meirelles, O, Lyytikäinen, L-P, Polašek, O, Tanaka, T, Arking, DE, Ulivi, S, Trompet, S, Müller-Nurasyid, M, Smith, AV, Dörr, M, Kerr, KF, Magnani, JW, Del Greco M, F, Zhang, W, Nolte, IM, Silva, CT, Padmanabhan, S, Tragante, V, Esko, T, Abecasis, GR, Adriaens, ME, Andersen, K, Barnett, P, Bis, JC, Bodmer, R, Buckley, BM, Campbell, H, Cannon, MV, Chakravarti, A, Chen, LY, Delitala, A, Devereux, RB, Doevendans, PA, Dominiczak, AF, Ferrucci, L, Ford, I, Gieger, C, Harris, TB, Haugen, E, Heinig, M, Hernandez, DG, Hillege, HL, Hirschhorn, JN, Hofman, A, Hubner, N, Hwang, S-J, Iorio, A, Kähönen, M, Kellis, M, Kolcic, I, Kooner, IK, Kooner, JS, Kors, JA, Lakatta, EG, Lage, K, Launer, LJ, Levy, D, Lundby, A, Macfarlane, PW, May, D, Meitinger, T, Metspalu, A, Nappo, S, Naitza, S, Neph, S, Nord, AS, Nutile, T, Okin, PM, Olsen, JV, Oostra, BA, Penninger, JM, Pennacchio, LA, Pers, TH, Perz, S, Peters, A, Pinto, YM, Pfeufer, A, Pilia, MG, Pramstaller, PP, Prins, BP, Raitakari, OT, Raychaudhuri, S, Rice, KM, Rossin, EJ, Rotter, JI, Schafer, S, Schlessinger, D, Schmidt, CO, Sehmi, J, Silljé, HHW, Sinagra, G, Sinner, MF, Slowikowski, K, Soliman, EZ, Spector, TD, Spiering, W, Stamatoyannopoulos, JA, Stolk, RP, Strauch, K, Tan, S-T, Tarasov, KV, Trinh, B, Uitterlinden, AG, van den Boogaard, M, van Duijn, CM, van Gilst, WH, Viikari, JS, Visscher, PM, Vitart, V, Völker, U, Waldenberger, M, Weichenberger, CX, Westra, H-J, Wijmenga, C, Wolffenbuttel, BH, Yang, J, Bezzina, CR, Munroe, PB, Snieder, H, Wright, AF, Rudan, I, Boyer, LA, Asselbergs, FW, van Veldhuisen, DJ, Stricker, BH, Psaty, BM, Ciullo, M, Sanna, S, Lehtimäki, T, Wilson, JF, Bandinelli, S, Alonso, A, Gasparini, P, Jukema, JW, Kääb, S, Gudnason, V, Felix, SB, Heckbert, SR, de Boer, RA, Newton-Cheh, C, Hicks, AA, Chambers, JC, Jamshidi, Y, Visel, A, Christoffels, VM, Isaacs, A, Samani, NJ & de Bakker, PIW 2016, '52 Genetic Loci Influencing Myocardial Mass', Journal of the American College of Cardiology, vol. 68, no. 13, pp. 1435-48. https://doi.org/10.1016/j.jacc.2016.07.729

APA

van der Harst, P., van Setten, J., Verweij, N., Vogler, G., Franke, L., Maurano, M. T., Wang, X., Mateo Leach, I., Eijgelsheim, M., Sotoodehnia, N., Hayward, C., Sorice, R., Meirelles, O., Lyytikäinen, L-P., Polašek, O., Tanaka, T., Arking, D. E., Ulivi, S., Trompet, S., ... de Bakker, P. I. W. (2016). 52 Genetic Loci Influencing Myocardial Mass. Journal of the American College of Cardiology, 68(13), 1435-48. https://doi.org/10.1016/j.jacc.2016.07.729

Vancouver

van der Harst P, van Setten J, Verweij N, Vogler G, Franke L, Maurano MT et al. 52 Genetic Loci Influencing Myocardial Mass. Journal of the American College of Cardiology. 2016 Sep 27;68(13):1435-48. https://doi.org/10.1016/j.jacc.2016.07.729

Author

van der Harst, Pim ; van Setten, Jessica ; Verweij, Niek ; Vogler, Georg ; Franke, Lude ; Maurano, Matthew T ; Wang, Xinchen ; Mateo Leach, Irene ; Eijgelsheim, Mark ; Sotoodehnia, Nona ; Hayward, Caroline ; Sorice, Rossella ; Meirelles, Osorio ; Lyytikäinen, Leo-Pekka ; Polašek, Ozren ; Tanaka, Toshiko ; Arking, Dan E ; Ulivi, Sheila ; Trompet, Stella ; Müller-Nurasyid, Martina ; Smith, Albert V ; Dörr, Marcus ; Kerr, Kathleen F ; Magnani, Jared W ; Del Greco M, Fabiola ; Zhang, Weihua ; Nolte, Ilja M ; Silva, Claudia T ; Padmanabhan, Sandosh ; Tragante, Vinicius ; Esko, Tõnu ; Abecasis, Gonçalo R ; Adriaens, Michiel E ; Andersen, Karl ; Barnett, Phil ; Bis, Joshua C ; Bodmer, Rolf ; Buckley, Brendan M ; Campbell, Harry ; Cannon, Megan V ; Chakravarti, Aravinda ; Chen, Lin Y ; Delitala, Alessandro ; Devereux, Richard B ; Doevendans, Pieter A ; Dominiczak, Anna F ; Ferrucci, Luigi ; Ford, Ian ; Gieger, Christian ; Harris, Tamara B ; Haugen, Eric ; Heinig, Matthias ; Hernandez, Dena G ; Hillege, Hans L ; Hirschhorn, Joel N ; Hofman, Albert ; Hubner, Norbert ; Hwang, Shih-Jen ; Iorio, Annamaria ; Kähönen, Mika ; Kellis, Manolis ; Kolcic, Ivana ; Kooner, Ishminder K ; Kooner, Jaspal S ; Kors, Jan A ; Lakatta, Edward G ; Lage, Kasper ; Launer, Lenore J ; Levy, Daniel ; Lundby, Alicia ; Macfarlane, Peter W ; May, Dalit ; Meitinger, Thomas ; Metspalu, Andres ; Nappo, Stefania ; Naitza, Silvia ; Neph, Shane ; Nord, Alex S ; Nutile, Teresa ; Okin, Peter M ; Olsen, Jesper V ; Oostra, Ben A ; Penninger, Josef M ; Pennacchio, Len A ; Pers, Tune H ; Perz, Siegfried ; Peters, Annette ; Pinto, Yigal M ; Pfeufer, Arne ; Pilia, Maria Grazia ; Pramstaller, Peter P ; Prins, Bram P ; Raitakari, Olli T ; Raychaudhuri, Soumya ; Rice, Ken M ; Rossin, Elizabeth J ; Rotter, Jerome I ; Schafer, Sebastian ; Schlessinger, David ; Schmidt, Carsten O ; Sehmi, Jobanpreet ; Silljé, Herman H W ; Sinagra, Gianfranco ; Sinner, Moritz F ; Slowikowski, Kamil ; Soliman, Elsayed Z ; Spector, Timothy D ; Spiering, Wilko ; Stamatoyannopoulos, John A ; Stolk, Ronald P ; Strauch, Konstantin ; Tan, Sian-Tsung ; Tarasov, Kirill V ; Trinh, Bosco ; Uitterlinden, Andre G ; van den Boogaard, Malou ; van Duijn, Cornelia M ; van Gilst, Wiek H ; Viikari, Jorma S ; Visscher, Peter M ; Vitart, Veronique ; Völker, Uwe ; Waldenberger, Melanie ; Weichenberger, Christian X ; Westra, Harm-Jan ; Wijmenga, Cisca ; Wolffenbuttel, Bruce H ; Yang, Jian ; Bezzina, Connie R ; Munroe, Patricia B ; Snieder, Harold ; Wright, Alan F ; Rudan, Igor ; Boyer, Laurie A ; Asselbergs, Folkert W ; van Veldhuisen, Dirk J ; Stricker, Bruno H ; Psaty, Bruce M ; Ciullo, Marina ; Sanna, Serena ; Lehtimäki, Terho ; Wilson, James F ; Bandinelli, Stefania ; Alonso, Alvaro ; Gasparini, Paolo ; Jukema, J Wouter ; Kääb, Stefan ; Gudnason, Vilmundur ; Felix, Stephan B ; Heckbert, Susan R ; de Boer, Rudolf A ; Newton-Cheh, Christopher ; Hicks, Andrew A ; Chambers, John C ; Jamshidi, Yalda ; Visel, Axel ; Christoffels, Vincent M ; Isaacs, Aaron ; Samani, Nilesh J ; de Bakker, Paul I W. / 52 Genetic Loci Influencing Myocardial Mass. In: Journal of the American College of Cardiology. 2016 ; Vol. 68, No. 13. pp. 1435-48.

Bibtex

@article{c4d5e140655740919bfe5602a26cdfa6,
title = "52 Genetic Loci Influencing Myocardial Mass",
abstract = "BACKGROUND: Myocardial mass is a key determinant of cardiac muscle function and hypertrophy. Myocardial depolarization leading to cardiac muscle contraction is reflected by the amplitude and duration of the QRS complex on the electrocardiogram (ECG). Abnormal QRS amplitude or duration reflect changes in myocardial mass and conduction, and are associated with increased risk of heart failure and death.OBJECTIVES: This meta-analysis sought to gain insights into the genetic determinants of myocardial mass.METHODS: We carried out a genome-wide association meta-analysis of 4 QRS traits in up to 73,518 individuals of European ancestry, followed by extensive biological and functional assessment.RESULTS: We identified 52 genomic loci, of which 32 are novel, that are reliably associated with 1 or more QRS phenotypes at p < 1 × 10(-8). These loci are enriched in regions of open chromatin, histone modifications, and transcription factor binding, suggesting that they represent regions of the genome that are actively transcribed in the human heart. Pathway analyses provided evidence that these loci play a role in cardiac hypertrophy. We further highlighted 67 candidate genes at the identified loci that are preferentially expressed in cardiac tissue and associated with cardiac abnormalities in Drosophila melanogaster and Mus musculus. We validated the regulatory function of a novel variant in the SCN5A/SCN10A locus in vitro and in vivo.CONCLUSIONS: Taken together, our findings provide new insights into genes and biological pathways controlling myocardial mass and may help identify novel therapeutic targets.",
author = "{van der Harst}, Pim and {van Setten}, Jessica and Niek Verweij and Georg Vogler and Lude Franke and Maurano, {Matthew T} and Xinchen Wang and {Mateo Leach}, Irene and Mark Eijgelsheim and Nona Sotoodehnia and Caroline Hayward and Rossella Sorice and Osorio Meirelles and Leo-Pekka Lyytik{\"a}inen and Ozren Pola{\v s}ek and Toshiko Tanaka and Arking, {Dan E} and Sheila Ulivi and Stella Trompet and Martina M{\"u}ller-Nurasyid and Smith, {Albert V} and Marcus D{\"o}rr and Kerr, {Kathleen F} and Magnani, {Jared W} and {Del Greco M}, Fabiola and Weihua Zhang and Nolte, {Ilja M} and Silva, {Claudia T} and Sandosh Padmanabhan and Vinicius Tragante and T{\~o}nu Esko and Abecasis, {Gon{\c c}alo R} and Adriaens, {Michiel E} and Karl Andersen and Phil Barnett and Bis, {Joshua C} and Rolf Bodmer and Buckley, {Brendan M} and Harry Campbell and Cannon, {Megan V} and Aravinda Chakravarti and Chen, {Lin Y} and Alessandro Delitala and Devereux, {Richard B} and Doevendans, {Pieter A} and Dominiczak, {Anna F} and Luigi Ferrucci and Ian Ford and Christian Gieger and Harris, {Tamara B} and Eric Haugen and Matthias Heinig and Hernandez, {Dena G} and Hillege, {Hans L} and Hirschhorn, {Joel N} and Albert Hofman and Norbert Hubner and Shih-Jen Hwang and Annamaria Iorio and Mika K{\"a}h{\"o}nen and Manolis Kellis and Ivana Kolcic and Kooner, {Ishminder K} and Kooner, {Jaspal S} and Kors, {Jan A} and Lakatta, {Edward G} and Kasper Lage and Launer, {Lenore J} and Daniel Levy and Alicia Lundby and Macfarlane, {Peter W} and Dalit May and Thomas Meitinger and Andres Metspalu and Stefania Nappo and Silvia Naitza and Shane Neph and Nord, {Alex S} and Teresa Nutile and Okin, {Peter M} and Olsen, {Jesper V} and Oostra, {Ben A} and Penninger, {Josef M} and Pennacchio, {Len A} and Pers, {Tune H} and Siegfried Perz and Annette Peters and Pinto, {Yigal M} and Arne Pfeufer and Pilia, {Maria Grazia} and Pramstaller, {Peter P} and Prins, {Bram P} and Raitakari, {Olli T} and Soumya Raychaudhuri and Rice, {Ken M} and Rossin, {Elizabeth J} and Rotter, {Jerome I} and Sebastian Schafer and David Schlessinger and Schmidt, {Carsten O} and Jobanpreet Sehmi and Sillj{\'e}, {Herman H W} and Gianfranco Sinagra and Sinner, {Moritz F} and Kamil Slowikowski and Soliman, {Elsayed Z} and Spector, {Timothy D} and Wilko Spiering and Stamatoyannopoulos, {John A} and Stolk, {Ronald P} and Konstantin Strauch and Sian-Tsung Tan and Tarasov, {Kirill V} and Bosco Trinh and Uitterlinden, {Andre G} and {van den Boogaard}, Malou and {van Duijn}, {Cornelia M} and {van Gilst}, {Wiek H} and Viikari, {Jorma S} and Visscher, {Peter M} and Veronique Vitart and Uwe V{\"o}lker and Melanie Waldenberger and Weichenberger, {Christian X} and Harm-Jan Westra and Cisca Wijmenga and Wolffenbuttel, {Bruce H} and Jian Yang and Bezzina, {Connie R} and Munroe, {Patricia B} and Harold Snieder and Wright, {Alan F} and Igor Rudan and Boyer, {Laurie A} and Asselbergs, {Folkert W} and {van Veldhuisen}, {Dirk J} and Stricker, {Bruno H} and Psaty, {Bruce M} and Marina Ciullo and Serena Sanna and Terho Lehtim{\"a}ki and Wilson, {James F} and Stefania Bandinelli and Alvaro Alonso and Paolo Gasparini and Jukema, {J Wouter} and Stefan K{\"a}{\"a}b and Vilmundur Gudnason and Felix, {Stephan B} and Heckbert, {Susan R} and {de Boer}, {Rudolf A} and Christopher Newton-Cheh and Hicks, {Andrew A} and Chambers, {John C} and Yalda Jamshidi and Axel Visel and Christoffels, {Vincent M} and Aaron Isaacs and Samani, {Nilesh J} and {de Bakker}, {Paul I W}",
note = "Copyright {\textcopyright} 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.",
year = "2016",
month = sep,
day = "27",
doi = "10.1016/j.jacc.2016.07.729",
language = "English",
volume = "68",
pages = "1435--48",
journal = "Journal of the American College of Cardiology",
issn = "0735-1097",
publisher = "Elsevier",
number = "13",

}

RIS

TY - JOUR

T1 - 52 Genetic Loci Influencing Myocardial Mass

AU - van der Harst, Pim

AU - van Setten, Jessica

AU - Verweij, Niek

AU - Vogler, Georg

AU - Franke, Lude

AU - Maurano, Matthew T

AU - Wang, Xinchen

AU - Mateo Leach, Irene

AU - Eijgelsheim, Mark

AU - Sotoodehnia, Nona

AU - Hayward, Caroline

AU - Sorice, Rossella

AU - Meirelles, Osorio

AU - Lyytikäinen, Leo-Pekka

AU - Polašek, Ozren

AU - Tanaka, Toshiko

AU - Arking, Dan E

AU - Ulivi, Sheila

AU - Trompet, Stella

AU - Müller-Nurasyid, Martina

AU - Smith, Albert V

AU - Dörr, Marcus

AU - Kerr, Kathleen F

AU - Magnani, Jared W

AU - Del Greco M, Fabiola

AU - Zhang, Weihua

AU - Nolte, Ilja M

AU - Silva, Claudia T

AU - Padmanabhan, Sandosh

AU - Tragante, Vinicius

AU - Esko, Tõnu

AU - Abecasis, Gonçalo R

AU - Adriaens, Michiel E

AU - Andersen, Karl

AU - Barnett, Phil

AU - Bis, Joshua C

AU - Bodmer, Rolf

AU - Buckley, Brendan M

AU - Campbell, Harry

AU - Cannon, Megan V

AU - Chakravarti, Aravinda

AU - Chen, Lin Y

AU - Delitala, Alessandro

AU - Devereux, Richard B

AU - Doevendans, Pieter A

AU - Dominiczak, Anna F

AU - Ferrucci, Luigi

AU - Ford, Ian

AU - Gieger, Christian

AU - Harris, Tamara B

AU - Haugen, Eric

AU - Heinig, Matthias

AU - Hernandez, Dena G

AU - Hillege, Hans L

AU - Hirschhorn, Joel N

AU - Hofman, Albert

AU - Hubner, Norbert

AU - Hwang, Shih-Jen

AU - Iorio, Annamaria

AU - Kähönen, Mika

AU - Kellis, Manolis

AU - Kolcic, Ivana

AU - Kooner, Ishminder K

AU - Kooner, Jaspal S

AU - Kors, Jan A

AU - Lakatta, Edward G

AU - Lage, Kasper

AU - Launer, Lenore J

AU - Levy, Daniel

AU - Lundby, Alicia

AU - Macfarlane, Peter W

AU - May, Dalit

AU - Meitinger, Thomas

AU - Metspalu, Andres

AU - Nappo, Stefania

AU - Naitza, Silvia

AU - Neph, Shane

AU - Nord, Alex S

AU - Nutile, Teresa

AU - Okin, Peter M

AU - Olsen, Jesper V

AU - Oostra, Ben A

AU - Penninger, Josef M

AU - Pennacchio, Len A

AU - Pers, Tune H

AU - Perz, Siegfried

AU - Peters, Annette

AU - Pinto, Yigal M

AU - Pfeufer, Arne

AU - Pilia, Maria Grazia

AU - Pramstaller, Peter P

AU - Prins, Bram P

AU - Raitakari, Olli T

AU - Raychaudhuri, Soumya

AU - Rice, Ken M

AU - Rossin, Elizabeth J

AU - Rotter, Jerome I

AU - Schafer, Sebastian

AU - Schlessinger, David

AU - Schmidt, Carsten O

AU - Sehmi, Jobanpreet

AU - Silljé, Herman H W

AU - Sinagra, Gianfranco

AU - Sinner, Moritz F

AU - Slowikowski, Kamil

AU - Soliman, Elsayed Z

AU - Spector, Timothy D

AU - Spiering, Wilko

AU - Stamatoyannopoulos, John A

AU - Stolk, Ronald P

AU - Strauch, Konstantin

AU - Tan, Sian-Tsung

AU - Tarasov, Kirill V

AU - Trinh, Bosco

AU - Uitterlinden, Andre G

AU - van den Boogaard, Malou

AU - van Duijn, Cornelia M

AU - van Gilst, Wiek H

AU - Viikari, Jorma S

AU - Visscher, Peter M

AU - Vitart, Veronique

AU - Völker, Uwe

AU - Waldenberger, Melanie

AU - Weichenberger, Christian X

AU - Westra, Harm-Jan

AU - Wijmenga, Cisca

AU - Wolffenbuttel, Bruce H

AU - Yang, Jian

AU - Bezzina, Connie R

AU - Munroe, Patricia B

AU - Snieder, Harold

AU - Wright, Alan F

AU - Rudan, Igor

AU - Boyer, Laurie A

AU - Asselbergs, Folkert W

AU - van Veldhuisen, Dirk J

AU - Stricker, Bruno H

AU - Psaty, Bruce M

AU - Ciullo, Marina

AU - Sanna, Serena

AU - Lehtimäki, Terho

AU - Wilson, James F

AU - Bandinelli, Stefania

AU - Alonso, Alvaro

AU - Gasparini, Paolo

AU - Jukema, J Wouter

AU - Kääb, Stefan

AU - Gudnason, Vilmundur

AU - Felix, Stephan B

AU - Heckbert, Susan R

AU - de Boer, Rudolf A

AU - Newton-Cheh, Christopher

AU - Hicks, Andrew A

AU - Chambers, John C

AU - Jamshidi, Yalda

AU - Visel, Axel

AU - Christoffels, Vincent M

AU - Isaacs, Aaron

AU - Samani, Nilesh J

AU - de Bakker, Paul I W

N1 - Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

PY - 2016/9/27

Y1 - 2016/9/27

N2 - BACKGROUND: Myocardial mass is a key determinant of cardiac muscle function and hypertrophy. Myocardial depolarization leading to cardiac muscle contraction is reflected by the amplitude and duration of the QRS complex on the electrocardiogram (ECG). Abnormal QRS amplitude or duration reflect changes in myocardial mass and conduction, and are associated with increased risk of heart failure and death.OBJECTIVES: This meta-analysis sought to gain insights into the genetic determinants of myocardial mass.METHODS: We carried out a genome-wide association meta-analysis of 4 QRS traits in up to 73,518 individuals of European ancestry, followed by extensive biological and functional assessment.RESULTS: We identified 52 genomic loci, of which 32 are novel, that are reliably associated with 1 or more QRS phenotypes at p < 1 × 10(-8). These loci are enriched in regions of open chromatin, histone modifications, and transcription factor binding, suggesting that they represent regions of the genome that are actively transcribed in the human heart. Pathway analyses provided evidence that these loci play a role in cardiac hypertrophy. We further highlighted 67 candidate genes at the identified loci that are preferentially expressed in cardiac tissue and associated with cardiac abnormalities in Drosophila melanogaster and Mus musculus. We validated the regulatory function of a novel variant in the SCN5A/SCN10A locus in vitro and in vivo.CONCLUSIONS: Taken together, our findings provide new insights into genes and biological pathways controlling myocardial mass and may help identify novel therapeutic targets.

AB - BACKGROUND: Myocardial mass is a key determinant of cardiac muscle function and hypertrophy. Myocardial depolarization leading to cardiac muscle contraction is reflected by the amplitude and duration of the QRS complex on the electrocardiogram (ECG). Abnormal QRS amplitude or duration reflect changes in myocardial mass and conduction, and are associated with increased risk of heart failure and death.OBJECTIVES: This meta-analysis sought to gain insights into the genetic determinants of myocardial mass.METHODS: We carried out a genome-wide association meta-analysis of 4 QRS traits in up to 73,518 individuals of European ancestry, followed by extensive biological and functional assessment.RESULTS: We identified 52 genomic loci, of which 32 are novel, that are reliably associated with 1 or more QRS phenotypes at p < 1 × 10(-8). These loci are enriched in regions of open chromatin, histone modifications, and transcription factor binding, suggesting that they represent regions of the genome that are actively transcribed in the human heart. Pathway analyses provided evidence that these loci play a role in cardiac hypertrophy. We further highlighted 67 candidate genes at the identified loci that are preferentially expressed in cardiac tissue and associated with cardiac abnormalities in Drosophila melanogaster and Mus musculus. We validated the regulatory function of a novel variant in the SCN5A/SCN10A locus in vitro and in vivo.CONCLUSIONS: Taken together, our findings provide new insights into genes and biological pathways controlling myocardial mass and may help identify novel therapeutic targets.

U2 - 10.1016/j.jacc.2016.07.729

DO - 10.1016/j.jacc.2016.07.729

M3 - Journal article

C2 - 27659466

VL - 68

SP - 1435

EP - 1448

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

SN - 0735-1097

IS - 13

ER -

ID: 166504690