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


Iglesias, AI and Mishra, A and Vitart, V and Bykhovskaya, Y and Hohn, R and Springelkamp, H and Cuellar-Partida, G and Gharahkhani, P and Bailey, JNC and Willoughby, CE and Li, X and Yazar, S and Nag, A and Khawaja, AP and Polasek, O and Siscovick, D and Mitchell, P and Tham, YC and Haines, JL and Kearns, LS and Hayward, C and Shi, Y and van Leeuwen, EM and Taylor, KD and Bonnemaijer, P and Rotter, JI and Martin, NG and Zeller, T and Mills, RA and Staffieri, SE and Jonas, JB and Schmidtmann, I and Boutin, T and Kang, JH and Lucas, SE and Wong, TY and Beutel, ME and Wilson, JF and Uitterlinden, AG and Vithana, EN and Foster, PJ and Hysi, PG and Hewitt, AW and Khor, CC and Pasquale, LR and Montgomery, GW and Klaver, CCW and Aung, T and Pfeiffer, N and Mackey, DA and Hammond, CJ and Cheng, C-Y and Craig, JE and Rabinowitz, YS and Wiggs, JL and Burdon, KP and van Duijn, CM and MacGregor, S, Blue Mountains Eye Study—GWAS group, NEIGHBORHOOD Consortium, Wellcome Trust Case Control Consortium 2 (WTCCC2), Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases, Nature Communications, 9, (1) Article 1864. ISSN 2041-1723 (2018) [Refereed Article]


Copyright Statement

© 2018 The Authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0)

DOI: doi:10.1038/s41467-018-03646-6


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.

Item Details

Item Type:Refereed Article
Keywords:cornea, keratoconus, glaucoma, association
Research Division:Biomedical and Clinical Sciences
Research Group:Ophthalmology and optometry
Research Field:Ophthalmology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Lucas, SE (Dr Sionne Lucas)
UTAS Author:Hewitt, AW (Professor Alex Hewitt)
UTAS Author:Burdon, KP (Professor Kathryn Burdon)
ID Code:126984
Year Published:2018
Funding Support:National Health and Medical Research Council (1059954)
Web of Science® Times Cited:49
Deposited By:Menzies Institute for Medical Research
Deposited On:2018-07-06
Last Modified:2022-08-25
Downloads:98 View Download Statistics

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