rs11129176 (RARB): Optic Disc Area Genetic Variant

Key takeaways

• rs11129176 near the RARB gene is linked to optic disc area (the total size of the optic nerve head) in a GWAS of over 17,000 people.
• The genetic signal replicated in a separate group of nearly 7,000 individuals of Asian ancestry, supporting cross-population relevance.
• Optic disc area is highly heritable (estimated 52-83%) and is used clinically in glaucoma screening and monitoring.
• RARB was one of 10 newly identified gene regions for disc area in this study, expanding the known genetic architecture of optic nerve head morphology.

What the research says A 2015 meta-analysis by the International Glaucoma Genetics Consortium identified RARB as one of 10 novel genetic loci associated with optic disc area (the total size of the optic nerve head), discovered in 17,248 individuals of European ancestry across seven cohorts and replicated in 6,841 individuals of Asian ancestry across four cohorts PMID 26087016. Optic disc morphology is used clinically to predict risk for primary open-angle glaucoma (POAG, the most prevalent form of glaucoma and a leading cause of irreversible blindness), and the heritability of disc area alone is estimated at 52-83% PMID 26087016. A subsequent 2017 meta-analysis by the same consortium identified six additional novel loci for disc area using a larger imputation panel and validated findings in POAG case-control cohorts; whether RARB was separately confirmed in that analysis is not specified in the available text PMID 28449038.

Reported associations

• Optic disc area: rs11129176, near the RARB gene, was identified as one of 10 novel genetic loci associated with optic disc area in a two-stage GWAS meta-analysis (17,248 European-ancestry individuals in discovery, 6,841 Asian-ancestry individuals in replication); specific p-values and effect sizes for this variant are not available in the provided study text PMID 26087016.

Evidence quality The primary evidence for rs11129176 comes from a single meta-analysis (Springelkamp et al., 2015) encompassing 17,248 individuals of European ancestry across seven cohorts in discovery and 6,841 individuals of Asian ancestry across four cohorts in replication PMID 26087016. Cross-ancestry replication in a distinct population provides meaningful support for the validity of the finding. Effect sizes and p-values specific to rs11129176 are not reported in the available study text, limiting quantitative appraisal. The genotyping used HapMap Phase 2 imputation, which has since been superseded by denser reference panels in more recent GWAS. A 2017 follow-up meta-analysis from the same consortium used 1000 Genomes imputation and identified additional novel disc area loci, though it does not specifically address rs11129176 in the available text PMID 28449038. No conflicting findings are present in the provided studies. Whether this specific variant has been explicitly confirmed or refined in more recent, larger-sample analyses is not documented in the materials provided here; the evidence should be considered preliminary.

Lifestyle considerations No lifestyle considerations on file for this variant.