Genetic Determinants of Electrocardiographic P-Wave Duration and Relation to Atrial Fibrillation

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Genetic Determinants of Electrocardiographic P-Wave Duration and Relation to Atrial Fibrillation. / Weng, Lu Chen; Hall, Amelia Weber; Choi, Seung Hoan; Jurgens, Sean J.; Haessler, Jeffrey; Bihlmeyer, Nathan A.; Grarup, Niels; Lin, Honghuang; Teumer, Alexander; Li-Gao, Ruifang; Yao, Jie; Guo, Xiuqing; Brody, Jennifer A.; Müller-Nurasyid, Martina; Schramm, Katharina; Verweij, Niek; van den Berg, Marten E.; van Setten, Jessica; Isaacs, Aaron; Ramírez, Julia; Warren, Helen R.; Padmanabhan, Sandosh; Kors, Jan A.; de Boer, Rudolf A.; van der Meer, Peter; Sinner, Moritz F.; Waldenberger, Melanie; Psaty, Bruce M.; Taylor, Kent D.; Völker, Uwe; Kanters, Jørgen K.; Li, Man; Alonso, Alvaro; Perez, Marco V.; Vaartjes, Ilonca; Bots, Michiel L.; Huang, Paul L.; Heckbert, Susan R.; Lin, Henry J.; Kornej, Jelena; Munroe, Patricia B.; van Duijn, Cornelia M.; Asselbergs, Folkert W.; Stricker, Bruno H.; van der Harst, Pim; Kääb, Stefan; Peters, Annette; Sotoodehnia, Nona; Rotter, Jerome I.; Mook-Kanamori, Dennis O.; Dörr, Marcus; Felix, Stephan B.; Linneberg, Allan; Hansen, Torben; Arking, Dan E.; Kooperberg, Charles; Benjamin, Emelia J.; Lunetta, Kathryn L.; Ellinor, Patrick T.; Lubitz, Steven A.

In: Circulation. Genomic and precision medicine, Vol. 13, No. 5, 2020, p. 387-395.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Weng, LC, Hall, AW, Choi, SH, Jurgens, SJ, Haessler, J, Bihlmeyer, NA, Grarup, N, Lin, H, Teumer, A, Li-Gao, R, Yao, J, Guo, X, Brody, JA, Müller-Nurasyid, M, Schramm, K, Verweij, N, van den Berg, ME, van Setten, J, Isaacs, A, Ramírez, J, Warren, HR, Padmanabhan, S, Kors, JA, de Boer, RA, van der Meer, P, Sinner, MF, Waldenberger, M, Psaty, BM, Taylor, KD, Völker, U, Kanters, JK, Li, M, Alonso, A, Perez, MV, Vaartjes, I, Bots, ML, Huang, PL, Heckbert, SR, Lin, HJ, Kornej, J, Munroe, PB, van Duijn, CM, Asselbergs, FW, Stricker, BH, van der Harst, P, Kääb, S, Peters, A, Sotoodehnia, N, Rotter, JI, Mook-Kanamori, DO, Dörr, M, Felix, SB, Linneberg, A, Hansen, T, Arking, DE, Kooperberg, C, Benjamin, EJ, Lunetta, KL, Ellinor, PT & Lubitz, SA 2020, 'Genetic Determinants of Electrocardiographic P-Wave Duration and Relation to Atrial Fibrillation', Circulation. Genomic and precision medicine, vol. 13, no. 5, pp. 387-395. https://doi.org/10.1161/CIRCGEN.119.002874

APA

Weng, L. C., 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., Müller-Nurasyid, M., Schramm, K., Verweij, N., van den Berg, M. E., van Setten, J., Isaacs, A., ... Lubitz, S. A. (2020). Genetic Determinants of Electrocardiographic P-Wave Duration and Relation to Atrial Fibrillation. Circulation. Genomic and precision medicine, 13(5), 387-395. https://doi.org/10.1161/CIRCGEN.119.002874

Vancouver

Weng LC, Hall AW, Choi SH, Jurgens SJ, Haessler J, Bihlmeyer NA et al. Genetic Determinants of Electrocardiographic P-Wave Duration and Relation to Atrial Fibrillation. Circulation. Genomic and precision medicine. 2020;13(5):387-395. https://doi.org/10.1161/CIRCGEN.119.002874

Author

Weng, Lu Chen ; Hall, Amelia Weber ; Choi, Seung Hoan ; Jurgens, Sean J. ; Haessler, Jeffrey ; Bihlmeyer, Nathan A. ; Grarup, Niels ; Lin, Honghuang ; Teumer, Alexander ; Li-Gao, Ruifang ; Yao, Jie ; Guo, Xiuqing ; Brody, Jennifer A. ; Müller-Nurasyid, Martina ; Schramm, Katharina ; Verweij, Niek ; van den Berg, Marten E. ; van Setten, Jessica ; Isaacs, Aaron ; Ramírez, Julia ; Warren, Helen R. ; Padmanabhan, Sandosh ; Kors, Jan A. ; de Boer, Rudolf A. ; van der Meer, Peter ; Sinner, Moritz F. ; Waldenberger, Melanie ; Psaty, Bruce M. ; Taylor, Kent D. ; Völker, Uwe ; Kanters, Jørgen K. ; Li, Man ; Alonso, Alvaro ; Perez, Marco V. ; Vaartjes, Ilonca ; Bots, Michiel L. ; Huang, Paul L. ; Heckbert, Susan R. ; Lin, Henry J. ; Kornej, Jelena ; Munroe, Patricia B. ; van Duijn, Cornelia M. ; Asselbergs, Folkert W. ; Stricker, Bruno H. ; van der Harst, Pim ; Kääb, Stefan ; Peters, Annette ; Sotoodehnia, Nona ; Rotter, Jerome I. ; Mook-Kanamori, Dennis O. ; Dörr, Marcus ; Felix, Stephan B. ; Linneberg, Allan ; Hansen, Torben ; Arking, Dan E. ; Kooperberg, Charles ; Benjamin, Emelia J. ; Lunetta, Kathryn L. ; Ellinor, Patrick T. ; Lubitz, Steven A. / Genetic Determinants of Electrocardiographic P-Wave Duration and Relation to Atrial Fibrillation. In: Circulation. Genomic and precision medicine. 2020 ; Vol. 13, No. 5. pp. 387-395.

Bibtex

@article{efc7ea6310e14b3c941dc74b66294bab,
title = "Genetic Determinants of Electrocardiographic P-Wave Duration and Relation to Atrial Fibrillation",
abstract = "BACKGROUND: The P-wave duration (PWD) is an electrocardiographic 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, 5681 African, 1186 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 sequence kernel association tests examined low-frequency variant-PWD associations. Additionally, we examined the associations between PWD loci and AF using previous AF genome-wide association studies. 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 (eg, 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.",
keywords = "atrial fibrillation, electrophysiology, exome, genetic, genome-wide association studies, population",
author = "Weng, {Lu Chen} and Hall, {Amelia Weber} and Choi, {Seung Hoan} and Jurgens, {Sean J.} and Jeffrey Haessler and Bihlmeyer, {Nathan A.} and Niels Grarup and Honghuang Lin and Alexander Teumer and Ruifang Li-Gao and Jie Yao and Xiuqing Guo and Brody, {Jennifer A.} and Martina M{\"u}ller-Nurasyid and Katharina Schramm and Niek Verweij and {van den Berg}, {Marten E.} and {van Setten}, Jessica and Aaron Isaacs and Julia Ram{\'i}rez and Warren, {Helen R.} and Sandosh Padmanabhan and Kors, {Jan A.} and {de Boer}, {Rudolf A.} and {van der Meer}, Peter and Sinner, {Moritz F.} and Melanie Waldenberger and Psaty, {Bruce M.} and Taylor, {Kent D.} and Uwe V{\"o}lker and Kanters, {J{\o}rgen K.} and Man Li and Alvaro Alonso and Perez, {Marco V.} and Ilonca Vaartjes and Bots, {Michiel L.} and Huang, {Paul L.} and Heckbert, {Susan R.} and Lin, {Henry J.} and Jelena Kornej and Munroe, {Patricia B.} and {van Duijn}, {Cornelia M.} and Asselbergs, {Folkert W.} and Stricker, {Bruno H.} and {van der Harst}, Pim and Stefan K{\"a}{\"a}b and Annette Peters and Nona Sotoodehnia and Rotter, {Jerome I.} and Mook-Kanamori, {Dennis O.} and Marcus D{\"o}rr and Felix, {Stephan B.} and Allan Linneberg and Torben Hansen and Arking, {Dan E.} and Charles Kooperberg and Benjamin, {Emelia J.} and Lunetta, {Kathryn L.} and Ellinor, {Patrick T.} and Lubitz, {Steven A.}",
year = "2020",
doi = "10.1161/CIRCGEN.119.002874",
language = "English",
volume = "13",
pages = "387--395",
journal = "Circulation. Genomic and precision medicine",
issn = "2574-8300",
publisher = "American Heart Association",
number = "5",

}

RIS

TY - JOUR

T1 - Genetic Determinants of Electrocardiographic P-Wave Duration and Relation to Atrial Fibrillation

AU - Weng, Lu Chen

AU - Hall, Amelia Weber

AU - Choi, Seung Hoan

AU - Jurgens, Sean J.

AU - Haessler, Jeffrey

AU - Bihlmeyer, Nathan A.

AU - Grarup, Niels

AU - Lin, Honghuang

AU - Teumer, Alexander

AU - Li-Gao, Ruifang

AU - Yao, Jie

AU - Guo, Xiuqing

AU - Brody, Jennifer A.

AU - Müller-Nurasyid, Martina

AU - Schramm, Katharina

AU - Verweij, Niek

AU - van den Berg, Marten E.

AU - van Setten, Jessica

AU - Isaacs, Aaron

AU - Ramírez, Julia

AU - Warren, Helen R.

AU - Padmanabhan, Sandosh

AU - Kors, Jan A.

AU - de Boer, Rudolf A.

AU - van der Meer, Peter

AU - Sinner, Moritz F.

AU - Waldenberger, Melanie

AU - Psaty, Bruce M.

AU - Taylor, Kent D.

AU - Völker, Uwe

AU - Kanters, Jørgen K.

AU - Li, Man

AU - Alonso, Alvaro

AU - Perez, Marco V.

AU - Vaartjes, Ilonca

AU - Bots, Michiel L.

AU - Huang, Paul L.

AU - Heckbert, Susan R.

AU - Lin, Henry J.

AU - Kornej, Jelena

AU - Munroe, Patricia B.

AU - van Duijn, Cornelia M.

AU - Asselbergs, Folkert W.

AU - Stricker, Bruno H.

AU - van der Harst, Pim

AU - Kääb, Stefan

AU - Peters, Annette

AU - Sotoodehnia, Nona

AU - Rotter, Jerome I.

AU - Mook-Kanamori, Dennis O.

AU - Dörr, Marcus

AU - Felix, Stephan B.

AU - Linneberg, Allan

AU - Hansen, Torben

AU - Arking, Dan E.

AU - Kooperberg, Charles

AU - Benjamin, Emelia J.

AU - Lunetta, Kathryn L.

AU - Ellinor, Patrick T.

AU - Lubitz, Steven A.

PY - 2020

Y1 - 2020

N2 - BACKGROUND: The P-wave duration (PWD) is an electrocardiographic 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, 5681 African, 1186 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 sequence kernel association tests examined low-frequency variant-PWD associations. Additionally, we examined the associations between PWD loci and AF using previous AF genome-wide association studies. 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 (eg, 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.

AB - BACKGROUND: The P-wave duration (PWD) is an electrocardiographic 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, 5681 African, 1186 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 sequence kernel association tests examined low-frequency variant-PWD associations. Additionally, we examined the associations between PWD loci and AF using previous AF genome-wide association studies. 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 (eg, 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.

KW - atrial fibrillation

KW - electrophysiology

KW - exome

KW - genetic

KW - genome-wide association studies

KW - population

U2 - 10.1161/CIRCGEN.119.002874

DO - 10.1161/CIRCGEN.119.002874

M3 - Journal article

C2 - 32822252

AN - SCOPUS:85094219796

VL - 13

SP - 387

EP - 395

JO - Circulation. Genomic and precision medicine

JF - Circulation. Genomic and precision medicine

SN - 2574-8300

IS - 5

ER -

ID: 251579122