rs12109259 (IRX2-DT/LINC01377): QT Interval Locus
Key takeaways
- This variant near long non-coding RNA genes IRX2-DT and LINC01377 was identified in a cardiac GWAS of over 250,000 people.
- The QT interval it is linked to measures the full electrical cycle of the heart's ventricles; when abnormal, it raises risk of serious arrhythmia.
- The same variant increases expression of a nearby gene specifically in testis tissue, based on GTEx data from 953 donors.
- No individual effect size for this variant was reported in available study excerpts, so its relative contribution to cardiac risk cannot be estimated from the data on file.
Key takeaways
- This variant sits within a region containing two long non-coding RNA genes, IRX2-DT and LINC01377, and was identified in a large multi-ancestry cardiac electrophysiology GWAS covering more than 250,000 individuals.
- The QT interval, the ECG measure this variant is linked to, reflects the full duration of ventricular electrical activity; prolonged or shortened QT is associated with potentially fatal arrhythmias.
- The alternate allele at this position also shows increased expression of a nearby gene (ENSG00000295848) specifically in testis tissue, based on GTEx v11 data from 953 donors.
- No specific effect size for rs12109259 alone is available in the provided study text, and no drug response or lifestyle data are on file for this variant.
What the research says A multi-ancestry GWAS of up to 252,977 participants identified 177 independent loci associated with the QT interval (the ECG measure spanning ventricular depolarization and repolarization), 156 loci for the JT interval (repolarization alone), and 121 loci for QRS duration (depolarization alone); the IRX2-DT and LINC01377 region was among the reported loci in this analysis. Separately, GTEx v11 expression data from 953 donors shows that the alternate allele at rs12109259 is associated with increased expression of ENSG00000295848 specifically in testis tissue (slope +0.30, p=4.6e-5) GTEx Portal.
Reported associations
- QT interval: The locus was identified through a multi-ancestry GWAS of up to 252,977 individuals; the QT interval, when abnormal, is associated with ventricular arrhythmia and sudden cardiac death. No per-variant odds ratio or beta coefficient for rs12109259 is given in the available study text.
- Testis gene expression (ENSG00000295848): The alternate allele is associated with increased expression of a gene at this locus in testis tissue (slope +0.30, p=4.6e-5) GTEx Portal.
Evidence quality The QT interval association derives from a well-powered multi-ancestry GWAS with up to 252,977 participants spanning European (84%), Hispanic/Latino (7.7%), African (6.7%), and South/South-East Asian ancestries, identifying 177 QT loci genome-wide. No per-variant p-value, effect size, or replication status for rs12109259 specifically is available in the study excerpts provided, so the individual-variant evidence strength cannot be fully characterized from the data on file. The GTEx cis-eQTL in testis is based on 953 donors at FDR<0.05; this type of data describes a regulatory gene-expression relationship and does not directly establish a clinical disease outcome.
Tissue-specific expression effects
- ENSG00000295848: The alternate allele of rs12109259 is associated with increased expression of this gene in testis tissue; no other tissues reached significance at FDR<0.05 in GTEx v11 GTEx Portal.
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What is rs12109259?
rs12109259 is a genetic variant located near two long non-coding RNA genes, IRX2-DT and LINC01377. It was identified in a large multi-ancestry genome-wide study focused on the QT interval, an ECG-based measure of cardiac electrical activity spanning more than 250,000 participants.
What is the QT interval and why does it matter genetically?
The QT interval is the segment on an ECG that covers the full electrical cycle of the heart's ventricles, spanning both the contraction phase (QRS duration) and the recovery phase (JT interval). Abnormally long or short QT is linked to potentially fatal heart rhythm disorders, which is why large genetic studies are conducted to find contributing variants.
What are IRX2-DT and LINC01377?
Both are long non-coding RNA genes. The 'LINC' in LINC01377 stands for Long INtergenic non-Coding RNA, and 'DT' in IRX2-DT indicates a divergent transcript near the IRX2 gene region. Their specific biological roles in cardiac or other tissues are not described in the studies currently on file for this variant.
Why does a cardiac variant affect gene expression in testis?
It is not uncommon for genetic variants to show expression effects across multiple tissues. The GTEx data shows this variant increases expression of a nearby gene in testis, but this does not establish a functional connection to heart rhythm and may reflect shared regulatory elements. The cardiac association and the testis eQTL finding should be considered independently.
How confident are researchers in the QT interval association for rs12109259?
The association comes from a well-powered GWAS of over 250,000 people, which is large by genomic standards. However, no per-variant effect size or replication data for rs12109259 specifically is available in the study text provided, so the strength of this individual association cannot be fully assessed from the data on file.