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, Jahrgang 10, Nr. 4, 08.2017.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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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 -