The cornea thins and bulges into a cone, and vision distorts. It starts in children and young adults and is one of the commonest reasons for a corneal transplant. The first large genetic study of it found collagen — the protein the cornea is built from.
The cornea is the clear dome at the front of the eye, and it does most of the eye's focusing. Its shape is what makes that work. In keratoconus the cornea loses rigidity, thins in one area and bulges forward into a cone, and vision becomes distorted in a way glasses correct poorly.
It typically begins in the teens or twenties, progresses for years and then usually stabilises. It is one of the commonest indications for corneal transplantation worldwide. And, until recently, its mechanism was described in the literature as unknown.
Every variant on this page comes from a single source: the first large-scale genome-wide association study of keratoconus, published in 2021, with 4,669 cases and 116,547 controls, identifying 36 loci.
A page resting on one paper is weaker than a page resting on several, and this one says so. What makes this paper worth resting on is that it is roughly an order of magnitude larger than the work before it, it is multi-ethnic — unusual, on a site that normally has to warn the opposite — and its conclusion can be checked against the gene list rather than taken on trust.
The study implicated corneal collagen matrix integrity and cell differentiation pathways as primary disease mechanisms.
Collagen is the protein the corneal stroma is built from — the layer that gives the dome its stiffness. A disease of a cornea losing rigidity turning out to be, in part, a disease of collagen is exactly the result that makes a genome-wide scan believable, because the method had no way of being steered towards it.
Among the genes this site holds under this trait are COL5A1 and COL12A1, both collagens, alongside KLF5 and RORA, which are transcription factors — the cell differentiation half of the same conclusion.
Positions joined since this page was written
What this is The text above discusses the variants this page was written around. Since then the catalogue has joined 24 more positions to it, by shared trait or shared paper. They are listed here by the paper each came from; the text does not describe them, and each variant page carries that study's own record.
Verma A et al. 2024, Science (New York, N.Y.) rs375290574 (near RDH8), rs544696584 (near ARHGEF37), rs962307678 (near PRR20A), rs192984922 (near DDX43P2), rs144619021 (near LINC02264), rs574177860 (SPRY4-AS1), rs181856846 (near HSBP1), rs567010138 (PSD3), rs575273090 (near LINC02063), rs373192492 (TMEM213), rs183801341 (LINC01876), rs532547695 (near HS3ST3B1) and 8 more — PMID:39024449
Xu L et al. 2024, Investigative ophthalmology & visual science rs2300163 (PTGER3), rs3743680 (CHTF8), rs1077435 (near EYA1) — PMID:38767907
Hardcastle AJ et al. 2021, Communications biology rs117905623 (near RNA5SP318) — PMID:33649486
Keratoconus is one of the few conditions on this site where the practical message is about when rather than whether.
It progresses during the years it is most treatable. Corneal cross-linking — a procedure that stiffens the cornea — is used to halt progression, and it works on progression rather than on damage already done. Which means the thing that changes an outcome is being seen by an ophthalmologist early, not knowing a genotype.
Worth knowing if you are reading this for a young person. Vision that changes quickly, a prescription that keeps needing to be updated, or glasses that no longer correct properly are the signs that get keratoconus looked for. It is diagnosed by measuring the shape of the cornea, which takes minutes. Nothing on this page detects it and nothing on this page should delay that appointment.
The catalogue also holds variants for corneal structure and for refractive error under their own traits. They are measurements of the same organ, and they are not this disease.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Keratoconus comes down to these specific, well-studied positions — not a diagnosis. 41 positions are linked to this page; the ones this page's own text discusses are shown first.
The studies behind these variants recruited participants from different ancestries — a result found in one population doesn't always transfer to another. Based on 18 of 41 linked studies with a resolved discovery ancestry.
Databases, guidelines and references
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Keratoconus. MyGeneLog™. https://www.mygenelog.com/conditions/keratoconus
No. It is diagnosed by measuring the shape of the cornea, which takes minutes and is non-invasive. The variants here each shift risk slightly and are not used as a screening test anywhere.
It is worth an eye examination rather than a new pair of glasses. Vision that changes quickly, or glasses that stop correcting properly, are among the signs that lead an optometrist or ophthalmologist to measure corneal shape. That is the useful step, and this page is not a substitute for it.
Because the cornea is built from collagen and keratoconus is a loss of corneal rigidity. The study implicated collagen matrix integrity and cell differentiation, and the gene list includes COL5A1 and COL12A1. A scan that could have returned anything returned the structural protein the disease is a failure of.
It is a limitation and the page says so. What makes this paper worth resting on is that it is the first large-scale study of this condition, roughly an order of magnitude larger than earlier work, multi-ethnic, and its conclusion is checkable against the genes it names.
Free to reuse. This page's text is original writing from freely-available research, licensed CC BY 4.0 — reuse it, including commercially, with attribution to MyGeneLog™. It's general research-derived information, not medical advice or a diagnosis — see Terms of Use.