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Fifteen Genetic Loci Associated With the Electrocardiographic P Wave

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

In: CIRC-CARDIOVASC GENE, Vol. 10, No. 4, 08.2017.

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

Harvard

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, Müller-Nurasyid, M, Müller, C, North, KE, Reiner, AP, Tinker, LF, Kors, JA, Teumer, A, Petersmann, A, Sinner, MF, Buzkova, P, Smith, JD, Van Wagoner, DR, Völker, U, Waldenberger, M, Peters, A, Meitinger, T, Limacher, MC, Wilhelmsen, KC, Psaty, BM, Hofman, A, Uitterlinden, A, Krijthe, BP, Zhang, Z-M, Schnabel, RB, Kääb, S, van Duijn, C, Rotter, JI, Sotoodehnia, N, Dörr, 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', CIRC-CARDIOVASC GENE, vol. 10, no. 4. https://doi.org/10.1161/CIRCGENETICS.116.001667

APA

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., Müller-Nurasyid, M., Müller, C., North, K. E., Reiner, A. P., Tinker, L. F., ... Ellinor, P. T. (2017). Fifteen Genetic Loci Associated With the Electrocardiographic P Wave. CIRC-CARDIOVASC GENE, 10(4). https://doi.org/10.1161/CIRCGENETICS.116.001667

Vancouver

Christophersen IE, Magnani JW, Yin X, Barnard J, Weng L-C, Arking DE et al. Fifteen Genetic Loci Associated With the Electrocardiographic P Wave. CIRC-CARDIOVASC GENE. 2017 Aug;10(4). https://doi.org/10.1161/CIRCGENETICS.116.001667

Bibtex

@article{de1a3caeeeee40baa68113ff015d7ac7,
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 (P<5×10-8) novel loci and replicated a prior association with SCN10A. We identified 3 loci at SCN5A, TBX5, and CAV1/CAV2 that were jointly associated with the PR interval, PR segment, and P-wave duration. We identified 6 novel loci in meta-analysis of P-wave terminal force. Four of the identified genetic loci were significantly associated with gene expression in 329 left atrial samples. Finally, we observed that some of the loci associated with the P wave were linked to overall atrial conduction, whereas others identified distinct phases of atrial conduction.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.",
keywords = "Arrhythmias, Cardiac/genetics, Caveolin 1/genetics, Caveolin 2/genetics, Electrocardiography, Genetic Loci, Genome-Wide Association Study, Genotype, Heart Atria/metabolism, Humans, NAV1.5 Voltage-Gated Sodium Channel/genetics, NAV1.8 Voltage-Gated Sodium Channel/genetics, T-Box Domain Proteins/genetics",
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 M{\"u}ller-Nurasyid and Christian M{\"u}ller 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 V{\"o}lker 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 K{\"a}{\"a}b and {van Duijn}, Cornelia and Rotter, {Jerome I} and Nona Sotoodehnia and Marcus D{\"o}rr 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}",
note = "{\textcopyright} 2017 American Heart Association, Inc.",
year = "2017",
month = aug,
doi = "10.1161/CIRCGENETICS.116.001667",
language = "English",
volume = "10",
journal = "CIRC-CARDIOVASC GENE",
issn = "1942-325X",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

RIS

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 - Müller-Nurasyid, Martina

AU - Müller, 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 - Völker, 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 - Kääb, Stefan

AU - van Duijn, Cornelia

AU - Rotter, Jerome I

AU - Sotoodehnia, Nona

AU - Dörr, 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

N1 - © 2017 American Heart Association, Inc.

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 (P<5×10-8) novel loci and replicated a prior association with SCN10A. We identified 3 loci at SCN5A, TBX5, and CAV1/CAV2 that were jointly associated with the PR interval, PR segment, and P-wave duration. We identified 6 novel loci in meta-analysis of P-wave terminal force. Four of the identified genetic loci were significantly associated with gene expression in 329 left atrial samples. Finally, we observed that some of the loci associated with the P wave were linked to overall atrial conduction, whereas others identified distinct phases of atrial conduction.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.

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 (P<5×10-8) novel loci and replicated a prior association with SCN10A. We identified 3 loci at SCN5A, TBX5, and CAV1/CAV2 that were jointly associated with the PR interval, PR segment, and P-wave duration. We identified 6 novel loci in meta-analysis of P-wave terminal force. Four of the identified genetic loci were significantly associated with gene expression in 329 left atrial samples. Finally, we observed that some of the loci associated with the P wave were linked to overall atrial conduction, whereas others identified distinct phases of atrial conduction.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.

KW - Arrhythmias, Cardiac/genetics

KW - Caveolin 1/genetics

KW - Caveolin 2/genetics

KW - Electrocardiography

KW - Genetic Loci

KW - Genome-Wide Association Study

KW - Genotype

KW - Heart Atria/metabolism

KW - Humans

KW - NAV1.5 Voltage-Gated Sodium Channel/genetics

KW - NAV1.8 Voltage-Gated Sodium Channel/genetics

KW - T-Box Domain Proteins/genetics

U2 - 10.1161/CIRCGENETICS.116.001667

DO - 10.1161/CIRCGENETICS.116.001667

M3 - SCORING: Journal article

C2 - 28794112

VL - 10

JO - CIRC-CARDIOVASC GENE

JF - CIRC-CARDIOVASC GENE

SN - 1942-325X

IS - 4

ER -