Common and Rare Coding Genetic Variation Underlying the Electrocardiographic PR Interval

Honghuang Lin, Jessica van Setten, Albert V. Smith, Nathan A. Bihlmeyer, Helen R. Warren, Jennifer A. Brody, Farid Radmanesh, Leanne Hall, Niels Grarup, Martina Mueller-Nurasyid, Thibaud Boutin, Niek Verweij, Henry J. Lin, Ruifang Li-Gao, Marten E. van den Berg, Jonathan Marten, Stefan Weiss, Bram P. Prins, Jeffrey Haessler, Leo-Pekka LyytikainenHao Mei, Tamara B. Harris, Lenore J. Launer, Man Li, Alvaro Alonso, Elsayed Z. Soliman, John M. Connell, Paul L. Huang, Lu-Chen Weng, Heather S. Jameson, William Hucker, Alan Hanley, Nathan R. Tucker, Yii-Der Ida Chen, Joshua C. Bis, Kenneth M. Rice, Colleen M. Sitlani, Jan A. Kors, Zhijun Xie, Chengping Wen, Jared W. Magnani, Christopher P. Nelson, Jorgen K. Kanters, Moritz F. Sinner, Konstantin Strauch, Rudolf A. de Boer, Peter van der Meer, Mark Eijgelsheim, Pim van der Harst, Folkert W. Asselbergs

Research output: Contribution to journalArticleAcademicpeer-review

5 Citations (Scopus)

Abstract

BACKGROUND: Electrical conduction from the cardiac sinoatrial node to the ventricles is critical for normal heart function. Genome-wide association studies have identified more than a dozen common genetic loci that are associated with PR interval. However, it is unclear whether rare and low-frequency variants also contribute to PR interval heritability.

METHODS: We performed large-scale meta-analyses of the PR interval that included 83 367 participants of European ancestry and 9436 of African ancestry. We examined both common and rare variants associated with the PR interval.

RESULTS: We identified 31 genetic loci that were significantly associated with PR interval after Bonferroni correction (P

CONCLUSIONS: We identified common variants at 11 novel loci and rare variants within 2 gene regions that were significantly associated with PR interval. Our findings provide novel insights to the current understanding of atrioventricular conduction, which is critical for cardiac activity and an important determinant of health.

Original languageEnglish
Article number002037
Number of pages11
JournalCirculation. Genomic and precision medicine
Volume11
Issue number5
DOIs
Publication statusPublished - May-2018

Keywords

  • atrioventricular node
  • genetic loci
  • genome-wide association study
  • LONG QT SYNDROME
  • GENOME-WIDE ASSOCIATION
  • SUDDEN CARDIAC DEATH
  • ATRIAL-FIBRILLATION
  • DILATED CARDIOMYOPATHY
  • QRS DURATION
  • SCN5A GENE
  • CONDUCTION
  • VARIANTS
  • SCN10A

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