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Abstract #77099 Published in IGR 19-3
Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases
Iglesias AI; Mishra A; Vitart V; Bykhovskaya Y; Höhn R; Springelkamp H; Cuellar-Partida G; Gharahkhani P; Bailey JNC; Willoughby CE; Li X; Yazar S; Nag A; Khawaja AP; Polašek O; Siscovick D; Mitchell P; Tham YC; Haines JL; Kearns LS; Hayward CNature communications 2018; 9: 1864
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) 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.
Full article
Classification:
3.4.1 Linkage studies (Part of: 3 Laboratory methods > 3.4 Molecular genetics)
2.2 Cornea (Part of: 2 Anatomical structures in glaucoma)
