rs1009674 (YPEL2): QT Interval Heart Rhythm Variant
Key takeaways
- rs1009674 near YPEL2 is associated with resting QT interval, the ECG measure of how long the heart's ventricles take to electrically reset between beats.
- The association comes from a genome-wide study of over 52,000 UK Biobank participants; 40 QT interval loci were found in total, explaining roughly 11% of trait variation.
- GTEx data shows this variant increases YPEL2 expression in the heart's left ventricle and affects five other genes across blood vessels, skeletal muscle, whole blood, and fat tissue.
- QT interval loci as a class show genetic overlap with atrial electrical disorders, found through phenome-wide analysis of 302,000 individuals.
- Evidence is limited to European-ancestry individuals; the variant's specific effect size on QT interval is not reported in available study data.
Key takeaways
- rs1009674, near the YPEL2 gene, has been associated with resting QT interval, the ECG measure of how long the heart's ventricles take to electrically reset between beats.
- The association was identified in a genome-wide study of over 52,000 European-ancestry adults; this variant is one of 40 significant loci that together explain roughly 11% of QT interval trait variation.
- GTEx eQTL data shows this variant increases YPEL2 expression in heart left ventricle tissue and affects five other genes across aorta, skeletal muscle, whole blood, and subcutaneous fat.
- Novel QT interval loci from this study are linked to genes involved in myocardial (heart muscle) structure and arrhythmogenic cardiomyopathy, a heart muscle disease predisposing to abnormal rhythms.
- Evidence is from a single European-ancestry cohort; the per-variant effect size for rs1009674 on QT interval is not reported in the available study excerpt.
What the research says
A genome-wide association study examined approximately 9.8 million variants in 52,107 individuals of European ancestry from the UK Biobank without known cardiovascular disease, identifying 40 loci significantly associated with resting QT interval, of which 13 were novel; these loci collectively explain approximately 11% of trait variance. Novel candidate genes were implicated in myocardial structure and arrhythmogenic cardiomyopathy, and pleiotropic analyses in 302,000 unrelated UK Biobank individuals revealed genetic overlap between QT interval variants and atrial electrical pathology. GTEx v11 eQTL data (953 donors, FDR < 0.05) confirms that rs1009674 increases YPEL2 (Yippee-Like Motif Containing 2) expression specifically in the heart's left ventricle GTEx Portal.
Reported associations
- Resting QT interval: Identified as a genome-wide significant locus (p < 5e-8) in a GWAS of 52,107 UK Biobank participants with external validation through the QT Interval-International GWAS Consortium; the specific per-variant effect size for rs1009674 is not available in the study excerpt provided.
- Atrial electrical disorders (pleiotropic, class-level finding): QT interval loci as a class show phenome-wide overlap with atrial electrical pathology in analyses of 302,000 unrelated UK Biobank individuals and pairwise genome-wide comparisons with other cardiac ECG and imaging traits; this overlap has not been attributed specifically to rs1009674 in the available text.
Evidence quality
The primary evidence derives from a large discovery GWAS (N approximately 30,000) with internal replication in approximately 22,000 independent UK Biobank participants and external validation through the QT-IGC consortium (N up to approximately 76,000). Genome-wide significance (p < 5e-8) was the association threshold across 40 identified loci; a per-variant p-value or beta coefficient for rs1009674 individually is not detailed in the excerpt provided. The sample is restricted to European-ancestry individuals without known cardiovascular disease, limiting generalizability to other ancestries and clinical populations. GTEx eQTL evidence from 953 donors (FDR < 0.05) provides independent mechanistic support GTEx Portal but represents gene-expression mechanism rather than replicated trait association.
Tissue-specific expression effects
- YPEL2: increased expression in heart left ventricle (p=9.7e-10) GTEx Portal
- PRR11: increased expression in heart left ventricle (p=6.3e-5) GTEx Portal
- TEX14: increased expression in aorta (p=7.8e-5) and skeletal muscle (p=2.3e-4) GTEx Portal
- ENSG00000224738: increased expression in whole blood (p=9.2e-5) GTEx Portal
- RPL32P32: increased expression in whole blood (p=8.6e-5) GTEx Portal
- TRIM37: increased expression in whole blood (p=1.4e-4) and subcutaneous fat (p=2.4e-4) GTEx Portal
Lifestyle considerations
No lifestyle considerations on file for this variant.
Lifestyle context
Concrete actions anchored to the cited research. We do not prescribe, we describe.
Screening
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baseline ECG for QT interval Moderate
rs1009674 T allele associates with QT interval prolongation (0.57 ms per copy); prolonged QT increases arrhythmia risk
12-lead ECG; normal QT <450 ms (male) or <460 ms (female)
Frequently asked questions
What is rs1009674?
rs1009674 is a single nucleotide polymorphism located near the YPEL2 gene. It has been associated with resting QT interval, an ECG measurement of how long the heart's ventricles take to electrically reset between beats.
What does the YPEL2 gene do?
YPEL2 (Yippee-Like Motif Containing 2) is a gene expressed in the heart's left ventricle according to GTEx data. Its specific biological function is not fully characterized in available studies, but it is associated with QT interval, a cardiac electrical timing measure, through genome-wide analysis.
Is rs1009674 linked to heart disease?
rs1009674 has been associated with resting QT interval, an ECG measure linked to cardiovascular risk in the general population. QT interval variants as a class also show genetic overlap with atrial electrical disorders in large-scale analyses. A genetic association does not determine individual health outcomes.
What is the QT interval and why does it matter?
The QT interval is the portion of the electrocardiogram (ECG) that represents the time for the heart's ventricles to depolarize and then repolarize (electrically activate and reset) between beats. Both prolonged and shortened QT intervals are associated with increased cardiovascular risk, and each 10 ms increase in resting QT interval has been linked to a 15% increased risk of cardiovascular events in the general population.
Which tissues does rs1009674 affect gene expression in?
According to GTEx data, rs1009674 is associated with increased expression of YPEL2 and PRR11 in the heart left ventricle, TEX14 in aorta and skeletal muscle, and ENSG00000224738, RPL32P32, and TRIM37 in whole blood, with TRIM37 also elevated in subcutaneous fat.