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

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2018
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Iglesias, A.I. and Mishra, A. and Vitart, V. and Bykhovskaya, Y. and Hohn, R. and Springelkamp, H. and Cuellar-Partida, G. and Gharahkhani, P. and Bailey, J.N.C. and Willoughby, C.E. and Li, X. and Yazar, S. and Nag, A. and Khawaja, A.P. and Pola??ek, O. and Siscovick, D. and Mitchell, P. and Tham, Y.C. and Haines, J.L. and Kearns, L.S. and Hayward, C. and Shi, Y. and Van Leeuwen, E.M. and Taylor, K.D. and Wang, J.J. and Rochtchina, E. and Attia, J. and Scott, R. and Holliday, E.G. and Baird, P.N. and Xie, J. and Inouye, M. and Viswanathan, A. and Sim, X. and Bonnemaijer, P. and Rotter, J.I. and Martin, N.G. and Zeller, T. and Mills, R.A. and Staffieri, S.E. and Jonas, J.B. and Schmidtmann, I. and Boutin, T. and Kang, J.H. and Lucas, S.E.M. and Wong, T.Y. and Beutel, M.E. and Wilson, J.F. and Allingham, R.R. and Brilliant, M.H. and Budenz, D.L. and Christen, W.G. and Fingert, J. and Friedman, D.S. and Gaasterland, D. and Gaasterland, T. and Hauser, M.A. and Kraft, P. and Lee, R.K. and Lichter, P.R. and Liu, Y. and Loomis, S.J. and Moroi, S.E. and Pericak-Vance, M.A. and Realini, A. and Richards, J.E. and Schuman, J.S. and Scott, W.K. and Singh, K. and Sit, A.J. and Vollrath, D. and Weinreb, R.N. and Wollstein, G. and Zack, D.J. and Zhang, K. and Donnelly, P. and Barroso, I. and Blackwell, J.M. and Bramon, E. and Brown, M.A. and Casas, J.P. and Corvin, A. and Deloukas, P. and Duncanson, A. and Jankowski, J. and Markus, H.S. and Mathew, C.G. and Palmer, C.N.A. and Plomin, R. and Rautanen, A. and Sawcer, S.J. and Trembath, R.C. and Wood, N.W. and Spencer, C.C.A. and Band, G. and Bellenguez, C. and Freeman, C. and Hellenthal, G. and Giannoulatou, E. and Pirinen, M. and Pearson, R. and Strange, A. and Su, Z. and Vukcevic, D. and Langford, C. and Hunt, S.E. and Edkins, S. and Gwilliam, R. and Blackburn, H. and Bumpstead, S.J. and Dronov, S. and Gillman, M. and Gray, E. and Hammond, N. and Jayakumar, A. and McCann, O.T. and Liddle, J. and Potter, S.C. and Ravindrarajah, R. and Ricketts, M. and Waller, M. and Weston, P. and Widaa, S. and Whittaker, P. and Uitterlinden, A.G. and Vithana, E.N. and Foster, P.J. and Hysi, P.G. and Hewitt, A.W. and Khor, C.C. and Pasquale, L.R. and Montgomery, G.W. and Klaver, C.C.W. and Aung, T. and Pfeiffer, N. and MacKey, D.A. and Hammond, C.J. and Cheng, C.-Y. and Craig, J.E. and Rabinowitz, Y.S. and Wiggs, J.L. and Burdon, K.P. and Van Duijn, C.M. and MacGregor, S., Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases, Nature Communications, 2018, 9, 1864
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Abstract:
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.
URI:
http://hdl.handle.net/2262/89881
Author's Homepage:
http://people.tcd.ie/acorvin
Author: CORVIN, AIDEN
Type of material:
Journal Article
URI:
http://hdl.handle.net/2262/89881
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Series/Report no:
Nature Communications;
9;
1;
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Full text available
Subject:
Central corneal thickness (CCT), Eye diseases, Genetic influences, Keratoconus, Glaucoma
DOI:
http://dx.doi.org/10.1038/s41467-018-03646-6
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