A 2010 study found central corneal thickness — a highly heritable measurement taken alongside every eye-pressure check — linked to collagen and connective-tissue genes including COL5A1 and ZNF469.
Central corneal thickness (CCT) is exactly what it sounds like: how thick the clear front surface of the eye is at its center, measured routinely in eye exams. It is one of the more highly heritable measurements in ophthalmology — identical twins resemble each other closely on this trait — and it matters clinically for a specific reason: eye-pressure readings (the standard glaucoma screening measurement) are influenced by how thick or thin the cornea is, so a clinician needs to know CCT to interpret an eye-pressure result correctly. A thin cornea is also, independently, a recognized risk factor for developing glaucoma.
Lu, Dimasi, Hysi et al. 2010 ran a genome-wide association study in 2,269 people from Croatian and Scottish populations. In the discovery stage, two loci reached genome-wide significance: rs12447690, near ZNF469, and rs3132306 (tagging the same signal as the paper's own lead SNP, rs1536482), near COL5A1 — collagen type V alpha 1, a gene that builds one of the structural collagen fibers giving the cornea its shape and strength. Only the ZNF469 signal replicated directly in a follow-up sample; the COL5A1 association needed a larger meta-analysis, combining this study with other published corneal-thickness GWAS data, before it reached genome-wide significance on its own. That same combined analysis added two further loci, near AVGR8 and reaching into AKAP13.
A much larger follow-up, Lu et al. 2013, meta-analysed more than 20,000 people across European and Asian populations and found 16 new genome-wide-significant loci for CCT. Two of them — FOXO1 and FNDC3B — also conferred meaningfully higher keratoconus risk in a separate case-control analysis of 874 cases and 6,085 controls, with the FOXO1 variant carrying an odds ratio of 1.62. This page's own rs2721051, near FOXO1, is the exact variant the paper names for that keratoconus association — nine of this page's variants come from this study.
The genes here are a different biological story from the ones on this site's glaucoma page, which are mostly about the fluid dynamics and drainage that set intraocular pressure. CCT genetics instead points toward the structural collagen and connective-tissue biology that determines how the cornea itself is built — a reminder that "eye disease genetics" isn't one pathway, even for two measurements taken in the same clinical visit.
Corneal thickness is measured directly with a quick, painless instrument (a pachymeter), not estimated from genotype. The variants on this page describe why corneal thickness varies between people; they are not used by any guideline to diagnose an eye condition or to substitute for an actual pachymetry reading.
A thin cornea is one recognized risk factor considered alongside eye pressure, optic nerve appearance, and other findings when assessing glaucoma risk — it is one input among several in an eye exam, not a standalone genetic test, and nothing here changes how CCT is measured or used clinically.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Central Corneal Thickness comes down to these specific, well-studied positions — not a diagnosis. 28 positions are linked to this page; the ones this page's own text discusses are shown first.
Databases, guidelines and references
CCT is how thick the clear front surface of the eye is at its center, measured routinely in eye exams. It is highly heritable and matters clinically because eye-pressure readings are influenced by corneal thickness.
Studying 2,269 people from Croatian and Scottish populations, it found genome-wide-significant associations near ZNF469 and COL5A1 (a structural collagen gene), plus two more loci, near AVGR8 and AKAP13, after a larger combined meta-analysis.
No. This page's genes point to structural collagen biology that shapes the cornea itself, while this site's glaucoma page covers genes involved in eye-pressure regulation — a different biological pathway, even though thin corneas are a recognized clinical risk factor for glaucoma.
No individual variant does. Corneal thickness is measured directly with a simple clinical instrument, not estimated from genotype, and these are population-level statistical findings.
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