Keratoconus is characterised by reduced rigidity of the cornea with distortion and focal thinning that causes blurred vision, however, the pathogenetic mechanisms are unknown. It can lead to severe visual morbidity in children and young adults and is a common indication for corneal transplantation worldwide. Here we report the first large scale genome-wide association study of keratoconus including 4,669 cases and 116,547 controls. We have identified significant association with 36 genomic loci that, for the first time, implicate both dysregulation of corneal collagen matrix integrity and cell differentiation pathways as primary disease-causing mechanisms. The results also suggest pleiotropy, with some disease mechanisms shared with other corneal diseases, such as Fuchs endothelial corneal dystrophy. The common variants associated with keratoconus explain 12.5% of the genetic variance, which shows potential for the future development of a diagnostic test to detect susceptibility to disease.

• MeSH
• Cell Differentiation * genetics   MeSH
• Genome-Wide Association Study MeSH
• Extracellular Matrix * metabolism   pathology   MeSH
• Phenotype MeSH
• Genetic Predisposition to Disease MeSH
• Genetic Loci * MeSH
• Risk Assessment MeSH
• Polymorphism, Single Nucleotide * MeSH
• Keratoconus * diagnosis   ethnology   genetics   metabolism   MeSH
• Collagen * metabolism   MeSH
• Humans MeSH
• Risk Factors MeSH
• Case-Control Studies MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Meta-Analysis MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH
• Geographicals
• Australia epidemiology   MeSH
• Europe epidemiology   MeSH
• Names of Substances
• Collagen * MeSH