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Genetic Determinants of Electrocardiographic P-wave Duration and Relation to Atrial Fibrillation. Circulation. Genomic and precision medicine Weng, L., Hall, A. W., Choi, S. H., Jurgens, S. J., Haessler, J., Bihlmeyer, N. A., Grarup, N., Lin, H., Teumer, A., Li-Gao, R., Yao, J., Guo, X., Brody, J. A., Muller-Nurasyid, M., Schramm, K., Verweij, N., van den Berg, M. E., van Setten, J., Isaacs, A., Ramirez, J., Warren, H. R., Padmanabhan, S., Kors, J. A., de Boer, R. A., van der Meer, P., Sinner, M. F., Waldenberger, M., Psaty, B. M., Taylor, K. D., Volker, U., Kanters, J. K., Li, M., Alonso, A., Perez, M. V., Vaartjes, I., Bots, M. L., Huang, P. L., Heckbert, S. R., Lin, H. J., Kornej, J., Munroe, P. B., van Duijn, C. M., Asselbergs, F. W., Stricker, B. H., van der Harst, P., Kaab, S., Peters, A., Sotoodehnia, N., Rotter, J. I., Mook-Kanamori, D. O., Dorr, M., Felix, S. B., Linneberg, A., Hansen, T., Arking, D. E., Kooperberg, C., Benjamin, E. J., Lunetta, K. L., Ellinor, P. T., Lubitz, S. A. 2020

Abstract

Background - The P-wave duration (PWD) is an electrocardiographic (ECG) measurement that represents cardiac conduction in the atria. Shortened or prolonged PWD is associated with atrial fibrillation (AF). We used exome chip data to examine the associations between common and rare variants with PWD. Methods - Fifteen studies comprising 64,440 individuals (56,943 European, 5,681 African, 1,186 Hispanic, 630 Asian), and ~230,000 variants were used to examine associations with maximum PWD across the 12-lead ECG. Meta-analyses summarized association results for common variants; gene-based burden and SKAT tests examined low-frequency variant-PWD associations. Additionally, we examined the associations between PWD loci and AF using previous AF GWAS. Results - We identified 21 common and low-frequency genetic loci (14 novel) associated with maximum PWD, including several AF loci (TTN, CAND2, SCN10A, PITX2, CAV1, SYNPO2L, SOX5, TBX5, MYH6, RPL3L). The top variants at known sarcomere genes (TTN, MYH6) were associated with longer PWD and increased AF risk. However, top variants at other loci (e.g., PITX2 and SCN10A) were associated with longer PWD but lower AF risk. Conclusions - Our results highlight multiple novel genetic loci associated with PWD, and underscore the shared mechanisms of atrial conduction and AF. Prolonged PWD may be an endophenotype for several different genetic mechanisms of AF.

View details for DOI 10.1161/CIRCGEN.119.002874

View details for PubMedID 32822252