rs12324079 (ANKRD34C-AS1): Central Corneal Thickness
Key takeaways
- rs12324079 lies within ANKRD34C-AS1, a long non-coding RNA gene, and was identified as associated with central corneal thickness.
- The finding comes from a 44,039-person multiethnic genome-wide study spanning four ethnic groups.
- Together with 97 other loci, this association helps explain 14.2% of corneal thickness variation, up from a prior baseline of 8.5%.
- Twenty of the 98 corneal-thickness loci in the same study also showed significant links to keratoconus, a cornea-thinning disorder.
- Genetic causal analysis in the same study found no evidence that thinner corneas directly cause primary open-angle glaucoma.
Key takeaways
- rs12324079 lies within ANKRD34C-AS1, a long non-coding RNA gene, and was identified as associated with central corneal thickness.
- The finding comes from a 44,039-person multiethnic genome-wide study spanning four ethnic groups.
- Together with 97 other loci, this association helps explain 14.2% of corneal thickness variation, up from a prior baseline of 8.5%.
- Twenty of the 98 corneal-thickness loci in the same study also showed significant links to keratoconus, a cornea-thinning disorder.
- Genetic causal analysis in the same study found no evidence that thinner corneas directly cause primary open-angle glaucoma.
What the research says rs12324079, located within ANKRD34C-AS1 (a long non-coding RNA locus, meaning it produces RNA but not protein), was identified as one of 98 genomic regions associated with central corneal thickness (CCT) - a highly heritable ocular trait with broad-sense heritability estimates of 0.68 to 0.95 - in a multiethnic meta-analysis of 44,039 individuals from four ethnic groups (non-Hispanic white, Hispanic/Latino, East Asian, and African American). The full panel of 98 loci, of which 41 were novel at the time of publication, collectively explained up to 14.2% of CCT variance, substantially increasing the prior explained variance of 8.5%. The same study applied two-sample Mendelian randomization - a statistical technique that uses genetic variants as natural experiments to probe causality - and found no evidence that genetically predicted thinner CCT causally raises the risk of primary open-angle glaucoma.
Reported associations
- Central corneal thickness (CCT): The locus was identified in a multiethnic GWAS (n = 44,039) as one of 98 regions associated with this measurement of the cornea's central thickness; all 98 loci together explain up to 14.2% of CCT variance.
- Keratoconus (indirect, via CCT loci overlap): Twenty of the 98 CCT-associated loci from the same study were significantly associated with keratoconus after Bonferroni correction (a standard statistical threshold adjustment for multiple comparisons); the available study text does not specify whether this locus is among those 20.
Evidence quality The discovery study was a large multiethnic meta-analysis (n = 44,039) combining data from the Genetic Epidemiology Research in Adult Health and Aging (GERA) cohort and the International Glaucoma Genetics Consortium, covering four ethnic groups. Inclusion of African American and Hispanic/Latino participants - groups underrepresented in earlier CCT genetics work - is a notable methodological strength. The study advanced explained variance for CCT from 8.5% to 14.2%, a meaningful gain for a highly polygenic (many-gene) trait. However, the available study text does not report variant-level statistics (such as the beta coefficient, p-value, or per-allele effect size) for rs12324079 specifically, nor does it describe the biological function of the ANKRD34C-AS1 lncRNA in corneal tissue. No independent replication data specific to this variant appear in the provided materials. The evidence that this locus influences CCT is therefore supported by a well-powered study but remains preliminary at the variant level.
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What is ANKRD34C-AS1 and what does it do?
ANKRD34C-AS1 is a long non-coding RNA gene, meaning it produces RNA molecules but does not code for a protein. Its specific role in corneal biology is not described in the available research.
Is rs12324079 linked to glaucoma?
The discovery study found no causal evidence that thinner corneas increase the risk of primary open-angle glaucoma. A separate locus (RAPSN rs3740685) was linked to glaucoma in the same study, but rs12324079 was not identified in that connection.
Is rs12324079 associated with keratoconus?
Twenty of the 98 corneal-thickness loci from the discovery study were also significantly linked to keratoconus, but the available research does not confirm whether rs12324079 is among those 20.
How was rs12324079 discovered?
It was identified through a genome-wide association study (GWAS) - a large-scale scan of genetic variants across the genome - involving 44,039 participants from four ethnic backgrounds. The study found 98 total loci associated with corneal thickness, 41 of which were novel.
How reliable is the evidence linking rs12324079 to corneal thickness?
The evidence comes from a well-powered, ethnically diverse study, which is a methodological strength. However, variant-level statistics and independent replication specific to rs12324079 are not available in the reviewed materials, so the evidence is considered preliminary at the variant level.