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 journalArticleAcademicpeer-review

25 Citations (Web of Science)

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 languageEnglish
Article number001667
Number of pages57
JournalCirculation : Cardiovascular Genetics
Volume10
Issue number4
DOIs
Publication statusPublished - 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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