@article {8452,
	title = {{Genetic Determinants of Electrocardiographic P-wave Duration and Relation to Atrial Fibrillation},
	journal = {Circ Genom Precis Med},
	year = {2020},
	month = {Aug},
	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.},
	author = {Weng, L. C. and Hall, A. W. and Choi, S. H. and Jurgens, S. J. and Haessler, J. and Bihlmeyer, N. A. and Grarup, N. and Lin, H. and Teumer, A. and Li-Gao, R. and Yao, J. and Guo, X. and Brody, J. A. and M?ller-Nurasyid, M. and Schramm, K. and Verweij, N. and van den Berg, M. E. and van Setten, J. and Isaacs, A. and Ram?rez, J. and Warren, H. R. and Padmanabhan, S. and Kors, J. A. and de Boer, R. A. and van der Meer, P. and Sinner, M. F. and Waldenberger, M. and Psaty, B. M. and Taylor, K. D. and V?lker, U. and Kanters, J. K. and Li, M. and Alonso, A. and Perez, M. V. and Vaartjes, I. and Bots, M. L. and Huang, P. L. and Heckbert, S. R. and Lin, H. J. and Kornej, J. and Munroe, P. B. and van Duijn, C. M. and Asselbergs, F. W. and Stricker, B. H. and van der Harst, P. and K??b, S. and Peters, A. and Sotoodehnia, N. and Rotter, J. I. and Mook-Kanamori, D. O. and D?rr, M. and Felix, S. B. and Linneberg, A. and Hansen, T. and Arking, D. E. and Kooperberg, C. and Benjamin, E. J. and Lunetta, K. L. and Ellinor, P. T. and Lubitz, S. A.}
}
@article {8829,
	title = {{Rare Coding Variants Associated With Electrocardiographic Intervals Identify Monogenic Arrhythmia Susceptibility Genes: A Multi-Ancestry Analysis},
	journal = {Circ Genom Precis Med},
	volume = {14},
	year = {2021},
	month = {Aug},
	pages = {e003300},
	abstract = {Alterations in electrocardiographic (ECG) intervals are well-known markers for arrhythmia and sudden cardiac death (SCD) risk. While the genetics of arrhythmia syndromes have been studied, relations between electrocardiographic intervals and rare genetic variation at a population level are poorly understood.\ Using a discovery sample of 29 000 individuals with whole-genome sequencing from Trans-Omics in Precision Medicine and replication in nearly 100 000 with whole-exome sequencing from the UK Biobank and MyCode, we examined associations between low-frequency and rare coding variants with 5 routinely measured electrocardiographic traits (RR, P-wave, PR, and QRS intervals and corrected QT interval).\ ), a marker of SCD risk. Incomplete penetrance of such deleterious variation was common as over 70\% of carriers had normal electrocardiographic intervals.\ Our findings indicate that large-scale high-depth sequence data and electrocardiographic analysis identifies monogenic arrhythmia susceptibility genes and rare variants with large effects. Known pathogenic variation in conventional arrhythmia and SCD genes exhibited incomplete penetrance and accounted for only a small fraction of marked electrocardiographic interval prolongation.},
	author = {Choi, S. H. and Jurgens, S. J. and Haggerty, C. M. and Hall, A. W. and Halford, J. L. and Morrill, V. N. and Weng, L. C. and Lagerman, B. and Mirshahi, T. and Pettinger, M. and Guo, X. and Lin, H. J. and Alonso, A. and Soliman, E. Z. and Kornej, J. and Lin, H. and Moscati, A. and Nadkarni, G. N. and Brody, J. A. and Wiggins, K. L. and Cade, B. E. and Lee, J. and Austin-Tse, C. and Blackwell, T. and Chaffin, M. D. and Lee, C. J. and Rehm, H. L. and Roselli, C. and Redline, S. and Mitchell, B. D. and Sotoodehnia, N. and Psaty, B. M. and Heckbert, S. R. and Loos, R. J. F. and Vasan, R. S. and Benjamin, E. J. and Correa, A. and Boerwinkle, E. and Arking, D. E. and Rotter, J. I. and Rich, S. S. and Whitsel, E. A. and Perez, M. and Kooperberg, C. and Fornwalt, B. K. and Lunetta, K. L. and Ellinor, P. T. and Lubitz, S. A.}
}
