Identification of three novel genetic variations associated with electrocardiographic traits (QRS duration and PR interval) in East Asians

Hum Mol Genet. 2014 Dec 15;23(24):6659-67. doi: 10.1093/hmg/ddu374. Epub 2014 Jul 17.


The electrocardiogram has several advantages in detecting cardiac arrhythmia-it is readily available, noninvasive and cost-efficient. Recent genome-wide association studies have identified single-nucleotide polymorphisms that are associated with electrocardiogram measures. We performed a genome-wide association study using Korea Association Resource data for the discovery phase (Phase 1, n = 6805) and two consecutive replication studies in Japanese populations (Phase 2, n = 2285; Phase 3, n = 5010) for QRS duration and PR interval. Three novel loci were identified: rs2483280 (PRDM16 locus) and rs335206 (PRDM6 locus) were associated with QRS duration, and rs17026156 (SLC8A1 locus) correlated with PR interval. PRDM16 was recently identified as a causative gene of left ventricular non-compaction and dilated cardiomyopathy in 1p36 deletion syndrome, which is characterized by heart failure, arrhythmia and sudden cardiac death. Thus, our finding that a PRDM16 SNP is linked to QRS duration strongly implicates PRDM16 in cardiac function. In addition, C allele of rs17026156 increases PR interval (beta ± SE, 2.39 ± 0.40 ms) and exists far more frequently in East Asians (0.46) than in Europeans and Africans (0.05 and 0.08, respectively).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Arrhythmias, Cardiac / ethnology
  • Arrhythmias, Cardiac / genetics*
  • Arrhythmias, Cardiac / physiopathology
  • Asian People
  • DNA-Binding Proteins / genetics*
  • Electrocardiography
  • Female
  • Gene Frequency
  • Genome-Wide Association Study
  • Humans
  • Male
  • Middle Aged
  • Muscle Proteins / genetics*
  • Polymorphism, Single Nucleotide*
  • Quantitative Trait Loci*
  • Sodium-Calcium Exchanger / genetics*
  • Transcription Factors / genetics*


  • DNA-Binding Proteins
  • Muscle Proteins
  • PRDM16 protein, human
  • PRDM6 protein, human
  • Sodium-Calcium Exchanger
  • Transcription Factors
  • sodium-calcium exchanger 1