Expressive

rs10918594 (NOS1AP): Heart Shape Genetics

Key takeaways

  • rs10918594 near NOS1AP was linked to overall heart chamber shape in a cardiac MRI study of over 45,000 people
  • The alternate allele boosts NOS1AP expression specifically in the left ventricle, pointing to a molecular mechanism
  • A more ball-like (spherical) ventricular shape was associated with higher atrial fibrillation risk in this study
  • This is one of 43 genetic loci found for heart shape, 14 of which were newly discovered

Key takeaways

  • rs10918594 near NOS1AP was linked to overall heart chamber shape in a cardiac MRI study of over 45,000 people.
  • The alternate allele boosts NOS1AP expression specifically in the left ventricle, pointing to a molecular mechanism.
  • A more ball-like (spherical) ventricular shape was associated with higher atrial fibrillation risk in this study.
  • This is one of 43 genetic loci found for heart shape, 14 of which were newly discovered.

What the research says A genome-wide association study (GWAS) of multidimensional bi-ventricular heart shape used cardiovascular magnetic resonance (CMR) images from 45,683 UK Biobank participants, applying principal component analysis (PCA - a statistical method that compresses complex shape data into ranked axes of variation) across 11 components to identify 43 significant loci, including the OLFML2B (olfactomedin-like 2B) - NOS1AP (nitric oxide synthase 1 adapter protein) locus; 14 of these were previously unreported for cardiac traits. Genetically predicted shape scores were associated with cardiometabolic diseases, and the shape components reflecting more spherical ventricles (PCs 2 and 3) were specifically linked to increased atrial fibrillation risk. GTEx v11 eQTL (expression quantitative trait locus) data shows the alternate allele at this locus is associated with increased expression of both NOS1AP and a nearby gene, C1orf226, in the left ventricle and other heart and muscle tissues GTEx Portal.

Reported associations

  • Bi-ventricular heart shape (PCA-derived): rs10918594 was identified as a genome-wide significant locus for multidimensional heart shape measured by CMR in 45,683 UK Biobank participants; the specific principal component and per-allele effect size for this locus were not detailed in the provided study text.
  • Atrial fibrillation (study context): Within the same study, heart shape principal components associated with more spherical ventricles (PCs 2 and 3) were linked to increased atrial fibrillation risk; whether this locus specifically loads onto those shape components was not stated in the available text.

Evidence quality The heart shape GWAS used a large sample of 45,683 UK Biobank participants with CMR imaging, capturing 83.6% of shape variance across 11 principal components - a rigorous phenotyping approach for cardiac morphology. The study identified 43 genome-wide significant loci, 14 of which were previously unreported for cardiac traits, suggesting the methodology surfaced genuinely new biology. The GTEx eQTL associations for NOS1AP (p=3.7e-14 in left ventricle, 953 donors) and C1orf226 (p=5.3e-13 in left ventricle) are highly significant and provide strong support for regulatory effects at this locus GTEx Portal. However, the study text does not report the specific p-value, effect size, or principal component for rs10918594 individually, limiting single-locus assessment. No independent replication data for this locus specifically was provided, and its evidence should be treated as preliminary.

Tissue-specific expression effects

  • NOS1AP: The alternate allele is associated with increased expression in heart left ventricle, skeletal muscle, brain cerebellar hemisphere, and esophagus muscularis GTEx Portal.
  • C1orf226: The alternate allele is associated with increased expression in heart left ventricle, heart atrial appendage, esophagus muscularis, and skeletal muscle GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs10918594?

rs10918594 is a genetic variant located near the OLFML2B and NOS1AP genes on chromosome 1. It was identified as one of 43 genome-wide significant loci for bi-ventricular heart shape in a cardiac MRI study of over 45,000 people.

What does NOS1AP have to do with heart shape?

In tissue expression data from the GTEx project, the alternate allele at rs10918594 is associated with increased NOS1AP expression in the heart's left ventricle. The same variant was also identified in a large study linking genetic loci to how both heart chambers are shaped.

Is rs10918594 linked to atrial fibrillation?

Not directly. The study that identified this locus for heart shape found that specific shape patterns - more spherical ventricles - were associated with higher atrial fibrillation risk. Whether rs10918594 specifically drives those shape components was not stated in the available text.

What genes are near rs10918594?

rs10918594 is located near OLFML2B (olfactomedin-like 2B) and NOS1AP (nitric oxide synthase 1 adapter protein). GTEx expression data also shows the variant influences expression of a nearby gene, C1orf226, in heart tissue.

How strong is the evidence for rs10918594 and heart shape?

The heart shape study was large (45,683 participants) and methodologically rigorous, and the GTEx expression effects for NOS1AP and C1orf226 in heart tissue reach genome-wide significance. However, the specific p-value and effect size for rs10918594 individually were not reported in the available study text, so single-locus confidence remains limited pending replication.