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

Iglesias, Adriana I; Mishra, Aniket; Vitart, Veronique; Bykhovskaya, Yelena; Höhn, René Gerhard Joachim; 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, Yih Chung; Haines, Jonathan L; Kearns, Lisa S; ... (2018). Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases. Nature communications, 9(1), p. 1864. Nature Publishing Group 10.1038/s41467-018-03646-6

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Ophthalmology

UniBE Contributor:

Höhn, René Gerhard Joachim

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2041-1723

Publisher:

Nature Publishing Group

Language:

English

Submitter:

René Gerhard Joachim Höhn

Date Deposited:

04 Jun 2018 09:27

Last Modified:

04 Jun 2018 15:14

Publisher DOI:

10.1038/s41467-018-03646-6

PubMed ID:

29760442

BORIS DOI:

10.7892/boris.116838

URI:

https://boris.unibe.ch/id/eprint/116838

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