rs113040897 (LINC02488): Retinal Microvasculature GWAS

Key takeaways

• This variant, near the LINC02488 and TMEM161B genes, was identified as a novel genomic locus for retinal microvascular traits in a genome-wide study of over 54,000 UK Biobank participants.
• The retinal vascular traits linked to this locus are associated with future risk of hypertension, heart failure, type 2 diabetes, and kidney disease.
• The alternate allele at this locus is associated with increased expression of a nearby gene in breast mammary tissue, based on GTEx eQTL data.
• Evidence comes from a single large study; independent replication has not been reported in the available data.

What the research says A genome-wide association study (GWAS) using deep learning to analyze 97,895 retinal fundus photographs from 54,813 UK Biobank participants identified rs113040897, near LINC02488 and TMEM161B, as one of several novel genomic loci influencing retinal microvascular structure PMID 35862143. The study quantified two microvascular indices: vascular fractal dimension, a measure of how complex and branched the microvascular network is, and vascular density; genome-wide significant loci for these traits were enriched for pathways linked to angiogenesis, including vascular endothelial growth factor (VEGF), platelet-derived growth factor receptor, angiopoietin, and WNT signaling, as well as inflammation PMID 35862143. GTEx v11 eQTL data additionally show that the alternate allele at this locus is associated with increased expression of ENSG00000287862 in breast mammary tissue GTEx Portal.

Reported associations

• Retinal vascular structure: rs113040897 was identified as a novel GWAS locus for retinal microvascular indices across 97,895 fundus images from 54,813 UK Biobank participants; the specific index (fractal dimension or vascular density) is not specified in the available study text PMID 35862143.
• Cardiometabolic disease (indirect, via retinal phenotype): Low fractal dimension and low vascular density, the retinal traits at this locus, were significantly associated with higher incidence of hypertension, congestive heart failure, renal failure, type 2 diabetes, and sleep apnea over a median 10-year follow-up in the same cohort PMID 35862143.
• Ocular and other conditions (indirect, via retinal phenotype): Low fractal dimension and density were associated with incident mortality, anemia, and multiple ocular conditions; genetically lower microvascular density was independently associated with higher risk of retinal detachments and skin cancer in the same study PMID 35862143.

Evidence quality The GWAS was conducted in 54,813 UK Biobank participants using 97,895 retinal fundus images, making it one of the largest retinal vascular imaging studies to date PMID 35862143. The study identified 7 novel loci for fractal dimension and 13 for vascular density; rs113040897 is among these novel findings. No independent replication cohort is described in the available study text, and the specific effect size (beta coefficient or odds ratio) for this variant alone is not provided in the available excerpt. Phenome-wide analyses used a median 10-year follow-up period across 1,866 disease endpoints. Because this variant is a single-study discovery without documented replication, the evidence should be considered preliminary.

Tissue-specific expression effects

• ENSG00000287862: The alternate allele at this locus is associated with increased expression of this gene specifically in breast mammary tissue (p=9.3e-6, FDR < 0.05), based on GTEx v11 data across 953 donors GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.