Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases
AuthorIglesias, AI; Mishra, A; Vitart, V; Bykhovskaya, Y; Hoehn, R; Springelkamp, H; Cuellar-Partida, G; Gharahkhani, P; Bailey, JNC; Willoughby, CE; ...
Source TitleNature Communications
PublisherNATURE PUBLISHING GROUP
University of Melbourne Author/sWong, Tien; Mackey, David; Craig, Jamie; Hewitt, Alexander; STAFFIERI, SANDRA; Mitchell, Paul
AffiliationCentre for Eye Research Australia (CERA)
Medicine (Austin & Northern Health)
Ophthalmology (Eye & Ear Hospital)
Document TypeJournal Article
CitationsIglesias, A. I., Mishra, A., Vitart, V., Bykhovskaya, Y., Hoehn, R., Springelkamp, H., Cuellar-Partida, G., Gharahkhani, P., Bailey, J. N. C., Willoughby, C. E., Li, X., Yazar, S., Nag, A., Khawaja, A. P., Polasek, O., Siscovick, D., Mitchell, P., Tham, Y. C., Haines, J. L. ,... MacGregor, S. (2018). Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases. NATURE COMMUNICATIONS, 9 (1), https://doi.org/10.1038/s41467-018-03646-6.
Access StatusOpen Access
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.
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Publisher licenceCC BY
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