Expressive

rs11658767 (CALM2P1/CASC17): QTc Interval Variant

Key takeaways

  • Associated with QTc interval duration (the heart's electrical recharge time) in a GWAS of over 84,000 people
  • The alternate allele is linked to increased KCNJ2 gene expression in the heart atrial appendage
  • Both rare gene variants and common variants like this one contribute to QTc variation in the population
  • Evidence for this specific locus is limited to a single large study; variant-level effect sizes are not available in the current source
  • This locus falls within the CALM2P1 and CASC17 genomic region

Key takeaways

  • Associated with QTc interval duration (the heart's electrical recharge time) in a GWAS of over 84,000 people
  • The alternate allele is linked to increased KCNJ2 gene expression in the heart atrial appendage
  • Both rare gene variants and common variants like this one contribute to QTc variation in the population
  • Evidence for this specific locus is limited to a single large study; variant-level effect sizes are not available in the current source
  • This locus falls within the CALM2P1 and CASC17 genomic region

What the research says A GWAS of heart rate-corrected QT interval (QTc) - a measure of how long the heart's electrical system takes to reset between beats - in 84,630 UK Biobank participants identified 54 independent associated loci, with 21 novel loci discovered and 12 of those replicated in a second cohort of 26,976 participants PMID 35500213. The same study found that a polygenic score built from over 1.1 million common variants was significantly associated with QTc (1.4 ms change per decile, 95% CI 1.3-1.5, p=1.1e-196), underscoring the broad contribution of common variant loci - including this one - to QTc variation across the population PMID 35500213. GTEx v11 expression data from 953 donors link the alternate allele at this locus to increased KCNJ2 expression specifically in the heart atrial appendage (slope +0.22, p=1.2e-4) GTEx Portal.

Reported associations

  • QTc interval duration: identified among 54 loci associated with QTc in a GWAS of 84,630 UK Biobank participants; the per-allele effect size specific to rs11658767 is not reported in the available source text PMID 35500213
  • KCNJ2 gene expression (heart atrial appendage): the alternate allele is associated with increased KCNJ2 expression in cardiac tissue (slope +0.22, p=1.2e-4, FDR<0.05, GTEx v11, n=953 donors) GTEx Portal

Evidence quality The QTc association comes from a large discovery cohort (n=84,630) with replication attempted in a second cohort (n=26,976); 54 total loci were identified and 12 novel loci were replicated, but the available source text does not specify whether this particular locus was among the replicated novel loci or a previously known one PMID 35500213. No per-allele effect size or p-value for rs11658767 specifically is provided in the current source, limiting direct assessment of this variant's individual contribution. The supporting GTEx eQTL signal (p=1.2e-4, FDR<0.05, n=953 donors) is a tissue-level regulatory observation and does not establish a clinical outcome GTEx Portal. Overall, the evidence is preliminary: grounded in a well-powered study, but lacking variant-specific detail in the available material.

Tissue-specific expression effects

  • KCNJ2: the alternate allele is associated with increased expression in the heart atrial appendage GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is the QTc interval and why does it matter?

QTc (heart rate-corrected QT interval) measures how long the heart's electrical system takes to fire and reset between beats, as recorded on an electrocardiogram (ECG). Prolongation of this interval has been associated with a higher risk of cardiac arrhythmias and sudden cardiac death in research studies.

What genes are near rs11658767?

rs11658767 falls in a region containing CALM2P1 (calmodulin 2 pseudogene 1) and CASC17 (cancer susceptibility candidate 17). GTEx expression data also link this variant to KCNJ2, a gene expressed in the heart atrial appendage.

What did the QTc genome-wide study find about this locus?

A GWAS of 84,630 UK Biobank participants identified 54 loci associated with QTc, including this region. The study showed that a polygenic score spanning over 1.1 million common variants was associated with 1.4 ms change in QTc per decile, illustrating how common-variant loci like this one collectively shape heart rhythm in the population.

What does the GTEx data show for rs11658767?

GTEx v11 data from 953 donors show that the alternate allele of rs11658767 is associated with increased KCNJ2 expression in the heart atrial appendage (slope +0.22, p=1.2e-4, FDR less than 0.05). This is a gene-regulatory association and does not directly indicate a clinical outcome.

How strong is the evidence for rs11658767 and heart rhythm?

The evidence comes from a single large GWAS of over 84,000 people with replication tested in a second cohort, but variant-specific effect sizes and replication status for this particular locus are not detailed in the available source. The GTEx eQTL finding adds supporting molecular context. Overall, findings should be considered preliminary.