- Title
- Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases
- Creator
- Iglesias, Adriana I.; Mishra, Aniket; Vitart, Veronique; Bykhovskaya, Yelena; Höhn, René; Springelkamp, Henriët; Cuellar-Partida, Gabriel; Gharahkhani, Puya; Bailey, Jessica N. Cooke; Willoughby, Colin E.; Li, Xiaohui; Yazar, Seyhan; Nag, Abhishek; Khawaja, Anthony P.; Polašek, Ozren; Siscovick, David; Mitchell, Paul; Tham, Yin Chung; Haines, Jonathan L.; Kearns, Lisa S.; Hayward, Caroline; Shi, Yuan; van Leeuwen, Elisabeth M.; Taylor, Kent D.; Wang, Jie Jin; Rochtchina, Elena; Attia, John; Scott, Rodney; Holliday, Elizabeth G.; Baird, Paul N.; Xie, Jing; Inouye, Michael; Viswanathan, Ananth; Sim, Xueling; Bonnemaijer, Pieter; Rotter, Jerome I.; Martin, Nicholas G.; Zeller, Tanja; Mills, Richard A.; Staffieri, Sandra E.; Jonas, Jost B.; Schmidtmann, Irene; Boutin, Thibaud; Kang, Jae H.; Lucas, Sionne E. M.; Wong, Tien Yin; Beutel, Manfred E.; Wilson, James F.; Allingham, R. Rand; Brilliant, Murray H.; Budenz, Donald L.; Christen, William G.; Fingert, John; Friedman, David S.; Gaasterland, Douglas; Gaasterland, Terry; Hauser, Michael A.; Kraft, Peter; Lee, Richard K.; Lichter, Paul R.; Liu, Yutao; Loomis, Stephanie J.; Moroi, Sayoko E.; Pericak-Vance, Margaret A.; Realini, Anthony; Richards, Julia E.; Schuman, Joel S.; Scott, William K.; Singh, Kuldev; Sit, Arthur J.; Vollrath, Douglas; Weinreb, Robert N.; Wollstein, Gadi; Zack, Donald J.; Zhang, Kang
- Relation
- Nature Communications Vol. 9, Issue 1, no. 1864
- Publisher Link
- http://dx.doi.org/10.1038/s41467-018-03646-6
- Publisher
- Nature Publishing Group
- Resource Type
- journal article
- Date
- 2018
- Description
- 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.
- Subject
- genetics of the nervous system; genetics research; genome-wide association studies; hereditary eye disease
- Identifier
- http://hdl.handle.net/1959.13/1386224
- Identifier
- uon:32383
- Identifier
- ISSN:2041-1723
- Rights
- This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. © The Author(s) 2018
- Language
- eng
- Full Text
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