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Central corneal thickness (CCT) is a highly heritable trait associated with complex eye diseases such as keratoconus and glaucoma. We perform a genome-wide association meta-analysis of CCT and identify 19 novel regions. In addition to adding support for known connective tissue-related pathways, pathway analyses uncover previously unreported gene sets. Remarkably, >20% of the CCT-loci are near or within Mendelian disorder genes. These included FBN1, ADAMTS2 and TGFB2 which associate with connective tissue disorders (Marfan, Ehlers-Danlos and Loeys-Dietz syndromes), and the LUM-DCN-KERA gene complex involved in myopia, corneal dystrophies and cornea plana. Using index CCT-increasing variants, we find a significant inverse correlation in effect sizes between CCT and keratoconus (r = -0.62, P = 5.30 × 10-5) but not between CCT and primary open-angle glaucoma (r = -0.17, P = 0.2). Our findings provide evidence for shared genetic influences between CCT and keratoconus, and implicate candidate genes acting in collagen and extracellular matrix regulation.

Original publication




Journal article


Nat Commun

Publication Date





ADAMTS Proteins, Asian Continental Ancestry Group, Cornea, Corneal Diseases, Corneal Dystrophies, Hereditary, Decorin, Ehlers-Danlos Syndrome, European Continental Ancestry Group, Eye Diseases, Hereditary, Fibrillin-1, Gene Expression, Genome, Human, Genome-Wide Association Study, Glaucoma, Open-Angle, Humans, Keratoconus, Loeys-Dietz Syndrome, Lumican, Marfan Syndrome, Mendelian Randomization Analysis, Myopia, Polymorphism, Single Nucleotide, Proteoglycans, Quantitative Trait Loci, Quantitative Trait, Heritable, Transforming Growth Factor beta2