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ExomeChip-Wide Analysis of 95 626 Individuals Identifies 10 Novel Loci Associated With QT and JT Intervals.
Wednesday,2018-09-19 09:10 America/Los_Angeles — ecterry
| Title | ExomeChip-Wide Analysis of 95 626 Individuals Identifies 10 Novel Loci Associated With QT and JT Intervals. |
| Publication Type | Journal Article |
| Year of Publication | 2018 |
| Authors | Bihlmeyer, NA, Brody, JA, Smith, AVernon, Warren, HR, Lin, H, Isaacs, A, Liu, C-T, Marten, J, Radmanesh, F, Hall, LM, Grarup, N, Mei, H, Müller-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, Lyytikäinen, 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, J Jukema, W, Maan, AC, Stricker, BHC, Rivadeneira, F, Uitterlinden, A, Völker, U, Homuth, G, Völzke, H, Felix, SB, Mangino, M, Spector, TD, Bots, ML, Perez, M, Raitakari, OT, Kähönen, 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, Kääb, S, Polasek, O, van der Harst, P, Heckbert, SR, Rotter, JI, Mook-Kanamori, DO, Eijgelsheim, M, Dörr, M, Jamshidi, Y, Asselbergs, FW, Kooperberg, C, Lehtimäki, T, Arking, DE, Sotoodehnia, N |
| Journal | Circ Genom Precis Med |
| Volume | 11 |
| Issue | 1 |
| Pagination | e001758 |
| Date Published | 2018 Jan |
| ISSN | 2574-8300 |
| Abstract | <p><b>BACKGROUND: </b>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.</p><p><b>METHODS AND RESULTS: </b>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.</p><p><b>CONCLUSIONS: </b>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.</p> |
| DOI | 10.1161/CIRCGEN.117.001758 |
| Alternate Journal | Circ Genom Precis Med |
| PubMed ID | 29874175 |
| PubMed Central ID | PMC5992491 |
| Grant List | T32 GM007814 / GM / NIGMS NIH HHS / United States R01 DA006227 / DA / NIDA NIH HHS / United States R01 MH101782 / MH / NIMH NIH HHS / United States R01 MH101810 / MH / NIMH NIH HHS / United States R01 MH101819 / MH / NIMH NIH HHS / United States R01 DA033684 / DA / NIDA NIH HHS / United States R01 MH090936 / MH / NIMH NIH HHS / United States P30 DK063491 / DK / NIDDK NIH HHS / United States R01 MH090951 / MH / NIMH NIH HHS / United States R01 MH101820 / MH / NIMH NIH HHS / United States R01 MH101825 / MH / NIMH NIH HHS / United States R01 MH090948 / MH / NIMH NIH HHS / United States R01 MH090941 / MH / NIMH NIH HHS / United States R01 MH101822 / MH / NIMH NIH HHS / United States HHSN261200800001C / RC / CCR NIH HHS / United States R01 MH090937 / MH / NIMH NIH HHS / United States UL1 TR001881 / TR / NCATS NIH HHS / United States HHSN268201000029C / HL / NHLBI NIH HHS / United States HHSN261200800001E / CA / NCI NIH HHS / United States R01 MH101814 / MH / NIMH NIH HHS / United States R01 HL111089 / HL / NHLBI NIH HHS / United States R01 HL116747 / HL / NHLBI NIH HHS / United States |
ePub date:
18/01