Expressive

rs116202356 (DLEC1): QRS Duration Cardiac Variant

Key takeaways

  • rs116202356 is a rare coding variant (~1.5% frequency) in DLEC1, linked to shorter QRS duration on the ECG
  • A allele carriers have QRS intervals ~1.63 ms shorter, one of the largest single-variant effects seen for this heart measure
  • Discovery in 85,593 people and replication in ~111,000 more gives this finding strong statistical backing
  • GTEx data show the variant shifts expression of OXSR1, CTDSPL, and EXOG across muscle, blood, arteries, and pancreas
  • DLEC1 was known in cancer research; this evidence reveals an unexpected role in the heart's electrical system

Key takeaways

  • rs116202356 is a rare coding variant (~1.5% frequency) in DLEC1, linked to shorter QRS duration on the ECG.
  • A allele carriers have QRS intervals ~1.63 ms shorter, one of the largest single-variant effects seen for this heart measure.
  • Discovery in 85,593 people and replication in ~111,000 more gives this finding strong statistical backing.
  • GTEx data show the variant shifts expression of OXSR1, CTDSPL, and EXOG across muscle, blood, arteries, and pancreas.
  • DLEC1 was known in cancer research; this evidence reveals an unexpected role in the heart's electrical system.

What the research says rs116202356, at chromosomal band 3p22.2, is a low-frequency non-synonymous (protein-altering) variant in DLEC1 (Deleted in Lung and Esophageal Cancer 1), identified as one of ten novel genetic loci for QRS duration - the electrocardiographic measure of ventricular depolarization - in an exome-chip meta-analysis of 85,593 participants of combined European and African American ancestry PMID 29875467. The A allele (combined minor allele frequency ~1.5%) was associated with a reduction in QRS duration of approximately 1.63 milliseconds (β = −1.63, SE = 0.17; p = 1.23 × 10^-²^0), a notably large per-variant effect for a complex cardiac trait PMID 29875467. Prolonged QRS duration is an established independent predictor of mortality in both the general population and in individuals with cardiac disease PMID 29875467.

Reported associations

  • QRS duration (ventricular depolarization interval): The A allele was associated with shorter QRS duration (β = −1.63 ms, SE = 0.17; p = 1.23 × 10^-²^0; n = 85,593) in a combined European and African American discovery meta-analysis PMID 29875467.

Evidence quality The discovery p-value of 1.23 × 10^-²^0 far exceeds the genome-wide significance threshold of 5 × 10^-8, and the study employed a two-stage design with replication in up to 111,874 individuals from the UK Biobank and deCODE cohorts PMID 29875467. The variant's low frequency (cMAF ~1.5%) places it in the low-frequency coding category targeted by the Illumina HumanExome BeadChip, a class of variants not captured by standard genome-wide SNP arrays and therefore previously understudied for QRS duration PMID 29875467. The non-synonymous annotation confirms the variant directly alters the protein sequence of this gene, though the specific amino acid change and its functional consequence in cardiac tissue are not characterized in the provided literature PMID 29875467. No conflicting findings appear across the source data; statistical support is strong, but mechanistic understanding of how this locus affects ventricular conduction remains preliminary.

Tissue-specific expression effects

  • EXOG: The variant is associated with reduced expression in pancreatic tissue GTEx Portal.
  • OXSR1: The variant is associated with increased expression in skeletal muscle and whole blood GTEx Portal.
  • CTDSPL: The variant is associated with increased expression in tibial artery GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is DLEC1 and what does it have to do with the heart?

DLEC1 (Deleted in Lung and Esophageal Cancer 1) was first characterized as a candidate tumor suppressor gene on chromosome 3. Genetic evidence now connects it to ventricular electrical conduction, though the precise cardiac mechanism has not yet been described in the available research.

What is QRS duration and why does it matter?

QRS duration is the time recorded on an electrocardiogram for the heart's ventricles to receive and spread the electrical signal that triggers contraction. Longer QRS intervals are an independent predictor of mortality in both the general population and in people with cardiac disease.

Is rs116202356 a common variant?

No. The minor (A) allele has a frequency of approximately 1.5%, making this a low-frequency coding variant. Most people carry two copies of the more common G allele.

How large is the effect of rs116202356 on QRS duration?

Each A allele reduces QRS duration by approximately 1.63 milliseconds, with a p-value of 1.23 × 10^-²^0 in 85,593 participants. This is among the larger per-variant effects reported for this ECG measure.

Is rs116202356 linked to atrial fibrillation or ischemic heart disease?

Studies linking rs116202356 to cardiac electrical traits have focused specifically on QRS duration. An association with atrial fibrillation or ischemic heart disease has not been reported in the research described here.