van der Harst, P;
van Setten, J;
Verweij, N;
Vogler, G;
Franke, L;
Maurano, MT;
Wang, X;
Mateo Leach, I;
Eijgelsheim, M;
Sotoodehnia, N;
et al.
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, 68 (13).
pp. 1435-1448.
https://doi.org/10.1016/j.jacc.2016.07.729
SGUL Authors: Jamshidi, Yalda
|
PDF
Accepted Version
Available under License Creative Commons Attribution Non-commercial No Derivatives. Download (11MB) | Preview |
|
|
PDF (Supplementary Information)
Accepted Version
Available under License Creative Commons Attribution Non-commercial No Derivatives. Download (4MB) | Preview |
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.
Item Type: | Article | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Additional Information: | © 2016. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ | |||||||||
Keywords: | QRS, electrocardiogram, genetic association study, heart failure, left ventricular hypertrophy, electrocardiogram, genetic association study, heart failure, left ventricular hypertrophy, QRS, Cardiovascular System & Hematology, 1102 Cardiovascular Medicine And Haematology, 1117 Public Health And Health Services | |||||||||
SGUL Research Institute / Research Centre: | Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Cell Sciences (INCCCS) |
|||||||||
Journal or Publication Title: | Journal of The American College of Cardiology | |||||||||
Language: | ENG | |||||||||
Dates: |
|
|||||||||
Publisher License: | Creative Commons: Attribution-Noncommercial-No Derivative Works 4.0 | |||||||||
Projects: |
|
|||||||||
PubMed ID: | 27659466 | |||||||||
Web of Science ID: | WOS:000385933800009 | |||||||||
Go to PubMed abstract | ||||||||||
URI: | https://openaccess.sgul.ac.uk/id/eprint/108181 | |||||||||
Publisher's version: | https://doi.org/10.1016/j.jacc.2016.07.729 |
Statistics
Actions (login required)
![]() |
Edit Item |