Bihlmeyer, NA; Brody, JA; Smith, AV; Warren, HR; Lin, H; Isaacs, A; Liu, C-T; ... Sotoodehnia, N; + view all Bihlmeyer, NA; Brody, JA; Smith, AV; Warren, HR; Lin, H; Isaacs, A; Liu, C-T; Marten, J; Radmanesh, F; Hall, LM; Grarup, N; Mei, H; Muller-Nurasyid, M; Huffman, JE; Verweij, N; Guo, X; Yao, J; Li-Gao, R; van den Berg, M; Weiss, S; Prins, BP; van Setten, J; Haessler, J; Lyytikainen, L-P; Li, M; Alonso, A; Soliman, EZ; Bis, JC; Austin, T; Chen, Y-DI; Psaty, BM; Harrris, TB; Launer, LJ; Padmanabhan, S; Dominiczak, A; Huang, PL; Xie, Z; Ellinor, PT; Kors, JA; Campbell, A; Murray, AD; Nelson, CP; Tobin, MD; Bork-Jensen, J; Hansen, T; Pedersen, O; Linneberg, A; Sinner, MF; Peters, A; Waldenberger, M; Meitinger, T; Perz, S; Kolcic, I; Rudan, I; de Boer, RA; van der Meer, P; Lin, HJ; Taylor, KD; de Mutsert, R; Trompet, S; Jukema, JW; Maan, AC; Stricker, BHC; Rivadeneira, F; Uitterlinden, A; Volker, U; Homuth, G; Volzke, H; Felix, SB; Mangino, M; Spector, TD; Bots, ML; Perez, M; Raitakari, OT; Kahonen, M; Mononen, N; Gudnason, V; Munroe, PB; Lubitz, SA; van Duijn, CM; Newton-Cheh, CH; Hayward, C; Rosand, J; Samani, NJ; Kanters, JK; Wilson, JG; Kaab, S; Polasek, O; van der Harst, P; Heckbert, SR; Rotter, JI; Mook-Kanamori, DO; Eij-Gelsheim, M; Dorr, M; Jamshidi, Y; Asselbergs, FW; Kooperberg, C; Lehtimaki, T; Arking, DE; Sotoodehnia, N; - view fewer (2018) ExomeChip-Wide Analysis of 95 626 Individuals Identifies 10 Novel Loci Associated With QT and JT Intervals. Circulation: Genomic and Precision Medicine , 11 (1) , Article e001758. 10.1161/CIRCGEN.117.001758.

Preview

Text Asselbergs_ExomeChip-Wide Analysis of 95 626 Individuals Identifies 10 Novel Loci Associated With QT and JT Intervals_VoR.pdf - Published Version Download (3MB) | Preview

Abstract

BACKGROUND: QT interval, measured through a standard ECG, captures the time it takes for the cardiac ventricles to depolarize and repolarize. JT interval is the component of the QT interval that reflects ventricular repolarization alone. Prolonged QT interval has been linked to higher risk of sudden cardiac arrest. METHODS AND RESULTS: We performed an ExomeChip-wide analysis for both QT and JT intervals, including 209 449 variants, both common and rare, in 17 341 genes from the Illumina Infinium HumanExome BeadChip. We identified 10 loci that modulate QT and JT interval duration that have not been previously reported in the literature using single-variant statistical models in a meta-analysis of 95 626 individuals from 23 cohorts (comprised 83 884 European ancestry individuals, 9610 blacks, 1382 Hispanics, and 750 Asians). This brings the total number of ventricular repolarization associated loci to 45. In addition, our approach of using coding variants has highlighted the role of 17 specific genes for involvement in ventricular repolarization, 7 of which are in novel loci. CONCLUSIONS: Our analyses show a role for myocyte internal structure and interconnections in modulating QT interval duration, adding to previous known roles of potassium, sodium, and calcium ion regulation, as well as autonomic control. We anticipate that these discoveries will open new paths to the goal of making novel remedies for the prevention of lethal ventricular arrhythmias and sudden cardiac arrest.

Download activity - last month

Export as JSONXMLCSV

Download activity - last 12 months

Export as CSVJSONXML

Downloads by country - last 12 months

Export as CSVXMLJSON

Archive Staff Only

View Item