Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases

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Iglesias, Adriana
Mishra, Aniket
Vitart, Veronique
Bykhovskaya, Yelena
Hohn, Rene
Springelkamp, Henriet
Cuellar-Partida, Gabriel
Gharahkhani, Puya
Cooke Bailey, Jessica N
Willoughby, Colin E
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Springer Nature
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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Genetics of the nervous system, Genetics research, Genome-wide association studies, Hereditary eye disease
Iglesias, A. I., Mishra, A., Vitart, V., Bykhovskaya, Y., … Höhn, R. (2018). Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases. Nature Communications, 9(1).