Expressive

rs11865049 (SLC7A5): Central Serous Chorioretinopathy Risk

Key takeaways

  • rs11865049 near SLC7A5 on chromosome 16q24.2 is linked to roughly twice the odds of central serous chorioretinopathy, a retinal condition affecting middle-aged people.
  • The association reached genome-wide significance (P = 9.71 x 10^-9, odds ratio 2.10) across 320 Japanese CSC cases and 3,245 controls.
  • The variant is also associated with increased SLC7A5 expression in subcutaneous fat tissue and reduced expression of a neighboring gene in whole blood, per GTEx eQTL data.
  • Evidence is currently limited to a Japanese population and has not yet been replicated in other ancestries.

Key takeaways

  • rs11865049 near SLC7A5 on chromosome 16q24.2 is linked to roughly twice the odds of central serous chorioretinopathy, a retinal condition affecting middle-aged people.
  • The association reached genome-wide significance (P = 9.71 x 10^-9, odds ratio 2.10) across 320 Japanese CSC cases and 3,245 controls.
  • The variant is also associated with increased SLC7A5 expression in subcutaneous fat tissue and reduced expression of a neighboring gene in whole blood, per GTEx eQTL data.
  • Evidence is currently limited to a Japanese population and has not yet been replicated in other ancestries.

What the research says A two-stage genome-wide association study (GWAS) in a Japanese population identified rs11865049 at SLC7A5 on chromosome 16q24.2 as a novel susceptibility locus for central serous chorioretinopathy (CSC) - a retinal disorder that can impair vision in middle-aged individuals. The combined analysis of 320 idiopathic CSC cases and 3,245 population-based controls yielded a meta-analysis p-value of 9.71 x 10^-9 and an odds ratio of 2.10, indicating that carriers of the risk allele have roughly twice the odds of developing the condition. The authors concluded that SLC7A5 is a potential candidate gene for CSC, pointing to a previously unidentified molecular mechanism for the disorder.

Reported associations

  • Central serous chorioretinopathy (CSC): Risk-allele carriers showed approximately doubled odds of developing this retinal disorder (odds ratio 2.10, combined P = 9.71 x 10^-9) in a Japanese two-stage GWAS (320 cases, 3,245 controls).

Evidence quality The association clears the conventional genome-wide significance threshold of 5 x 10^-8, with a combined p-value of 9.71 x 10^-9 across 320 CSC cases and 3,245 controls, all of Japanese ancestry. The two-stage design included a discovery cohort (137 cases, 1,174 controls) followed by a replication cohort (183 cases, 2,071 controls), providing internal validation. However, the case count of 320 is modest, and no external replication in non-Japanese populations has been reported in the provided study. The evidence should be considered preliminary for populations outside Japan.

Tissue-specific expression effects

  • SLC7A5: The alternate allele at rs11865049 is associated with increased expression in subcutaneous adipose tissue GTEx Portal.
  • ENSG00000300742: The alternate allele is associated with reduced expression in whole blood 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

  • regular eye exams to monitor for central serous retinopathy Moderate

    carriers of the rs11865049 A allele have 2.1-fold increased risk of chronic central serous retinopathy

    discuss with ophthalmologist and establish appropriate screening interval

Frequently asked questions

What is central serous chorioretinopathy?

Central serous chorioretinopathy (CSC) is a retinal disorder in which fluid accumulates beneath the retina, often causing blurred or distorted vision. It most commonly affects middle-aged people, and its molecular causes were previously not well understood.

What is the SLC7A5 gene and why does rs11865049 matter?

SLC7A5 is a gene located at chromosome 16q24.2. A 2019 GWAS found that rs11865049, located at this gene, is a novel susceptibility locus for central serous chorioretinopathy, suggesting SLC7A5 plays a role in a previously uncharacterized molecular mechanism for the disorder.

How strong is the evidence linking rs11865049 to eye disease?

The variant reached genome-wide significance (P = 9.71 x 10^-9) with an odds ratio of 2.10 in a two-stage GWAS. However, all participants were of Japanese ancestry and the case count of 320 is modest, so the finding awaits replication in larger and more diverse populations.

Does rs11865049 affect gene expression?

GTEx eQTL data show that the alternate allele is linked to increased SLC7A5 expression in subcutaneous fat tissue and reduced expression of a neighboring gene (ENSG00000300742) in whole blood. These expression-level associations describe potential molecular mechanisms but do not directly establish disease causality.

Is rs11865049 associated with vision problems?

A GWAS identified rs11865049 as a susceptibility locus for central serous chorioretinopathy, a condition that can cause visual disturbance. Carriers of the risk allele had roughly twice the odds of the condition compared to non-carriers in a Japanese study population.