Fifteen Genetic Loci Associated With the Electrocardiographic P Wave

Ingrid E. Christophersen; Jared W. Magnani; Xiaoyan Yin; John Barnard; Lu-Chen Weng; Dan E. Arking; Maartje N. Niemeijer; Steven A. Lubitz; Christy L. Avery; Qing Duan; Stephan B. Felix; Joshua C. Bis; Kathleen F. Kerr; Aaron Isaacs; Martina Mueller-Nurasyid; Christian Mueller; Kari E. North; Alex P. Reiner; Lesley F. Tinker; Jan A. Kors; Alexander Teumer; Astrid Petersmann; Moritz F. Sinner; Petra Buzkova; Jonathan D. Smith; David R. Van Wagoner; Uwe Voelker; Melanie Waldenberger; Annette Peters; Thomas Meitinger; Marian C. Limacher; Kirk C. Wilhelmsen; Bruce M. Psaty; Albert Hofman; Andre Uitterlinden; Bouwe P. Krijthe; Zhu-Ming Zhang; Renate B. Schnabel; Stefan Kaeaeb; Cornelia van Duijn; Jerome I. Rotter; Nona Sotoodehnia; Marcus Doerr; Yun Li; Mina K. Chung; Elsayed Z. Soliman; Alvaro Alonso; Eric A. Whitsel; Bruno H. Stricker; Emelia J. Benjamin; Susan R. Heckbert; Patrick T. Ellinor

doi:10.1161/CIRCGENETICS.116.001667

Fifteen Genetic Loci Associated With the Electrocardiographic P Wave

Ingrid E. Christophersen, Jared W. Magnani^*, Xiaoyan Yin, John Barnard, Lu-Chen Weng, Dan E. Arking, Maartje N. Niemeijer, Steven A. Lubitz, Christy L. Avery, Qing Duan, Stephan B. Felix, Joshua C. Bis, Kathleen F. Kerr, Aaron Isaacs, Martina Mueller-Nurasyid, Christian Mueller, Kari E. North, Alex P. Reiner, Lesley F. Tinker, Jan A. KorsAlexander Teumer, Astrid Petersmann, Moritz F. Sinner, Petra Buzkova, Jonathan D. Smith, David R. Van Wagoner, Uwe Voelker, Melanie Waldenberger, Annette Peters, Thomas Meitinger, Marian C. Limacher, Kirk C. Wilhelmsen, Bruce M. Psaty, Albert Hofman, Andre Uitterlinden, Bouwe P. Krijthe, Zhu-Ming Zhang, Renate B. Schnabel, Stefan Kaeaeb, Cornelia van Duijn, Jerome I. Rotter, Nona Sotoodehnia, Marcus Doerr, Yun Li, Mina K. Chung, Elsayed Z. Soliman, Alvaro Alonso, Eric A. Whitsel, Bruno H. Stricker, Emelia J. Benjamin, Susan R. Heckbert, Patrick T. Ellinor^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Background-The P wave on an ECG is a measure of atrial electric function, and its characteristics may serve as predictors for atrial arrhythmias. Increased mean P-wave duration and P-wave terminal force traditionally have been used as markers for left atrial enlargement, and both have been associated with increased risk of atrial fibrillation. Here, we explore the genetic basis of P-wave morphology through meta-analysis of genome-wide association study results for P-wave duration and P-wave terminal force from 12 cohort studies.

Methods and Results-We included 44 456 individuals, of which 6778 (16%) were of African ancestry. Genotyping, imputation, and genome-wide association study were performed at each study site. Summary-level results were meta-analyzed centrally using inverse-variance weighting. In meta-analyses of P-wave duration, we identified 6 significant (P

Conclusions-We have identified 6 novel genetic loci associated with P-wave duration and 6 novel loci associated with P-wave terminal force. Future studies of these loci may aid in identifying new targets for drugs that may modify atrial conduction or treat atrial arrhythmias.

Original language	English
Article number	001667
Number of pages	57
Journal	Circulation : Cardiovascular Genetics
Volume	10
Issue number	4
DOIs	https://doi.org/10.1161/CIRCGENETICS.116.001667
Publication status	Published - Aug 2017

Keywords

arrhythmia
atrial function
electrocardiography
genetic variation
genome-wide association study
GENOME-WIDE ASSOCIATION
MYOSIN HEAVY-CHAIN
DOMAIN PROTEIN-1 EPAS1
RENAL-CELL CARCINOMA
SICK SINUS SYNDROME
RESTING HEART-RATE
ATRIAL-FIBRILLATION
ATHEROSCLEROSIS RISK
CARDIAC MYOCYTES
COMMON VARIANTS

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10.1161/CIRCGENETICS.116.001667

Cite this

Christophersen, I. E., Magnani, J. W., Yin, X., Barnard, J., Weng, L.-C., Arking, D. E., Niemeijer, M. N., Lubitz, S. A., Avery, C. L., Duan, Q., Felix, S. B., Bis, J. C., Kerr, K. F., Isaacs, A., Mueller-Nurasyid, M., Mueller, C., North, K. E., Reiner, A. P., Tinker, L. F., ... Ellinor, P. T. (2017). Fifteen Genetic Loci Associated With the Electrocardiographic P Wave. Circulation : Cardiovascular Genetics, 10(4), Article 001667. https://doi.org/10.1161/CIRCGENETICS.116.001667

@article{fe231c1b5cc145edad0fb40ca43801b3,

title = "Fifteen Genetic Loci Associated With the Electrocardiographic P Wave",

abstract = "Background-The P wave on an ECG is a measure of atrial electric function, and its characteristics may serve as predictors for atrial arrhythmias. Increased mean P-wave duration and P-wave terminal force traditionally have been used as markers for left atrial enlargement, and both have been associated with increased risk of atrial fibrillation. Here, we explore the genetic basis of P-wave morphology through meta-analysis of genome-wide association study results for P-wave duration and P-wave terminal force from 12 cohort studies.Methods and Results-We included 44 456 individuals, of which 6778 (16%) were of African ancestry. Genotyping, imputation, and genome-wide association study were performed at each study site. Summary-level results were meta-analyzed centrally using inverse-variance weighting. In meta-analyses of P-wave duration, we identified 6 significant (PConclusions-We have identified 6 novel genetic loci associated with P-wave duration and 6 novel loci associated with P-wave terminal force. Future studies of these loci may aid in identifying new targets for drugs that may modify atrial conduction or treat atrial arrhythmias.",

keywords = "arrhythmia, atrial function, electrocardiography, genetic variation, genome-wide association study, GENOME-WIDE ASSOCIATION, MYOSIN HEAVY-CHAIN, DOMAIN PROTEIN-1 EPAS1, RENAL-CELL CARCINOMA, SICK SINUS SYNDROME, RESTING HEART-RATE, ATRIAL-FIBRILLATION, ATHEROSCLEROSIS RISK, CARDIAC MYOCYTES, COMMON VARIANTS",

author = "Christophersen, {Ingrid E.} and Magnani, {Jared W.} and Xiaoyan Yin and John Barnard and Lu-Chen Weng and Arking, {Dan E.} and Niemeijer, {Maartje N.} and Lubitz, {Steven A.} and Avery, {Christy L.} and Qing Duan and Felix, {Stephan B.} and Bis, {Joshua C.} and Kerr, {Kathleen F.} and Aaron Isaacs and Martina Mueller-Nurasyid and Christian Mueller and North, {Kari E.} and Reiner, {Alex P.} and Tinker, {Lesley F.} and Kors, {Jan A.} and Alexander Teumer and Astrid Petersmann and Sinner, {Moritz F.} and Petra Buzkova and Smith, {Jonathan D.} and {Van Wagoner}, {David R.} and Uwe Voelker and Melanie Waldenberger and Annette Peters and Thomas Meitinger and Limacher, {Marian C.} and Wilhelmsen, {Kirk C.} and Psaty, {Bruce M.} and Albert Hofman and Andre Uitterlinden and Krijthe, {Bouwe P.} and Zhu-Ming Zhang and Schnabel, {Renate B.} and Stefan Kaeaeb and {van Duijn}, Cornelia and Rotter, {Jerome I.} and Nona Sotoodehnia and Marcus Doerr and Yun Li and Chung, {Mina K.} and Soliman, {Elsayed Z.} and Alvaro Alonso and Whitsel, {Eric A.} and Stricker, {Bruno H.} and Benjamin, {Emelia J.} and Heckbert, {Susan R.} and Ellinor, {Patrick T.}",

year = "2017",

month = aug,

doi = "10.1161/CIRCGENETICS.116.001667",

language = "English",

volume = "10",

journal = "Circulation : Cardiovascular Genetics",

issn = "1942-325X",

publisher = "LIPPINCOTT WILLIAMS & WILKINS",

number = "4",

}

Christophersen, IE, Magnani, JW, Yin, X, Barnard, J, Weng, L-C, Arking, DE, Niemeijer, MN, Lubitz, SA, Avery, CL, Duan, Q, Felix, SB, Bis, JC, Kerr, KF, Isaacs, A, Mueller-Nurasyid, M, Mueller, C, North, KE, Reiner, AP, Tinker, LF, Kors, JA, Teumer, A, Petersmann, A, Sinner, MF, Buzkova, P, Smith, JD, Van Wagoner, DR, Voelker, U, Waldenberger, M, Peters, A, Meitinger, T, Limacher, MC, Wilhelmsen, KC, Psaty, BM, Hofman, A, Uitterlinden, A, Krijthe, BP, Zhang, Z-M, Schnabel, RB, Kaeaeb, S, van Duijn, C, Rotter, JI, Sotoodehnia, N, Doerr, M, Li, Y, Chung, MK, Soliman, EZ, Alonso, A, Whitsel, EA, Stricker, BH, Benjamin, EJ, Heckbert, SR & Ellinor, PT 2017, 'Fifteen Genetic Loci Associated With the Electrocardiographic P Wave', Circulation : Cardiovascular Genetics, vol. 10, no. 4, 001667. https://doi.org/10.1161/CIRCGENETICS.116.001667

TY - JOUR

T1 - Fifteen Genetic Loci Associated With the Electrocardiographic P Wave

AU - Christophersen, Ingrid E.

AU - Magnani, Jared W.

AU - Yin, Xiaoyan

AU - Barnard, John

AU - Weng, Lu-Chen

AU - Arking, Dan E.

AU - Niemeijer, Maartje N.

AU - Lubitz, Steven A.

AU - Avery, Christy L.

AU - Duan, Qing

AU - Felix, Stephan B.

AU - Bis, Joshua C.

AU - Kerr, Kathleen F.

AU - Isaacs, Aaron

AU - Mueller-Nurasyid, Martina

AU - Mueller, Christian

AU - North, Kari E.

AU - Reiner, Alex P.

AU - Tinker, Lesley F.

AU - Kors, Jan A.

AU - Teumer, Alexander

AU - Petersmann, Astrid

AU - Sinner, Moritz F.

AU - Buzkova, Petra

AU - Smith, Jonathan D.

AU - Van Wagoner, David R.

AU - Voelker, Uwe

AU - Waldenberger, Melanie

AU - Peters, Annette

AU - Meitinger, Thomas

AU - Limacher, Marian C.

AU - Wilhelmsen, Kirk C.

AU - Psaty, Bruce M.

AU - Hofman, Albert

AU - Uitterlinden, Andre

AU - Krijthe, Bouwe P.

AU - Zhang, Zhu-Ming

AU - Schnabel, Renate B.

AU - Kaeaeb, Stefan

AU - van Duijn, Cornelia

AU - Rotter, Jerome I.

AU - Sotoodehnia, Nona

AU - Doerr, Marcus

AU - Li, Yun

AU - Chung, Mina K.

AU - Soliman, Elsayed Z.

AU - Alonso, Alvaro

AU - Whitsel, Eric A.

AU - Stricker, Bruno H.

AU - Benjamin, Emelia J.

AU - Heckbert, Susan R.

AU - Ellinor, Patrick T.

PY - 2017/8

Y1 - 2017/8

N2 - Background-The P wave on an ECG is a measure of atrial electric function, and its characteristics may serve as predictors for atrial arrhythmias. Increased mean P-wave duration and P-wave terminal force traditionally have been used as markers for left atrial enlargement, and both have been associated with increased risk of atrial fibrillation. Here, we explore the genetic basis of P-wave morphology through meta-analysis of genome-wide association study results for P-wave duration and P-wave terminal force from 12 cohort studies.Methods and Results-We included 44 456 individuals, of which 6778 (16%) were of African ancestry. Genotyping, imputation, and genome-wide association study were performed at each study site. Summary-level results were meta-analyzed centrally using inverse-variance weighting. In meta-analyses of P-wave duration, we identified 6 significant (PConclusions-We have identified 6 novel genetic loci associated with P-wave duration and 6 novel loci associated with P-wave terminal force. Future studies of these loci may aid in identifying new targets for drugs that may modify atrial conduction or treat atrial arrhythmias.

AB - Background-The P wave on an ECG is a measure of atrial electric function, and its characteristics may serve as predictors for atrial arrhythmias. Increased mean P-wave duration and P-wave terminal force traditionally have been used as markers for left atrial enlargement, and both have been associated with increased risk of atrial fibrillation. Here, we explore the genetic basis of P-wave morphology through meta-analysis of genome-wide association study results for P-wave duration and P-wave terminal force from 12 cohort studies.Methods and Results-We included 44 456 individuals, of which 6778 (16%) were of African ancestry. Genotyping, imputation, and genome-wide association study were performed at each study site. Summary-level results were meta-analyzed centrally using inverse-variance weighting. In meta-analyses of P-wave duration, we identified 6 significant (PConclusions-We have identified 6 novel genetic loci associated with P-wave duration and 6 novel loci associated with P-wave terminal force. Future studies of these loci may aid in identifying new targets for drugs that may modify atrial conduction or treat atrial arrhythmias.

KW - arrhythmia

KW - atrial function

KW - electrocardiography

KW - genetic variation

KW - genome-wide association study

KW - GENOME-WIDE ASSOCIATION

KW - MYOSIN HEAVY-CHAIN

KW - DOMAIN PROTEIN-1 EPAS1

KW - RENAL-CELL CARCINOMA

KW - SICK SINUS SYNDROME

KW - RESTING HEART-RATE

KW - ATRIAL-FIBRILLATION

KW - ATHEROSCLEROSIS RISK

KW - CARDIAC MYOCYTES

KW - COMMON VARIANTS

U2 - 10.1161/CIRCGENETICS.116.001667

DO - 10.1161/CIRCGENETICS.116.001667

M3 - Article

SN - 1942-325X

VL - 10

JO - Circulation : Cardiovascular Genetics

JF - Circulation : Cardiovascular Genetics

IS - 4

M1 - 001667

ER -