Ophthalmology (Eye & Ear Hospital) - Research Publications

Permanent URI for this collection

http://hdl.handle.net/11343/175

Filters

2020 - 2021 2
2
Reset filters

Settings
Statistics
Citations
Author: Baird, Paul × Author: Mitchell, Paul × End date: 2022 × Start date: 2020 ×

Search Results

Now showing 1 - 2 of 2
  • Item
    Thumbnail Image
    A multi-ethnic genome-wide association study implicates collagen matrix integrity and cell differentiation pathways in keratoconus
    Hardcastle, AJ ; Liskova, P ; Bykhovskaya, Y ; McComish, BJ ; Davidson, AE ; Inglehearn, CF ; Li, X ; Choquet, H ; Habeeb, M ; Lucas, SEM ; Sahebjada, S ; Pontikos, N ; Lopez, KER ; Khawaja, AP ; Ali, M ; Dudakova, L ; Skalicka, P ; Van Dooren, BTH ; Geerards, AJM ; Haudum, CW ; Lo Faro, V ; Tenen, A ; Simcoe, MJ ; Patasova, K ; Yarrand, D ; Yin, J ; Siddiqui, S ; Rice, A ; Farraj, LA ; Chen, Y-DI ; Rahi, JS ; Krauss, RM ; Theusch, E ; Charlesworth, JC ; Szczotka-Flynn, L ; Toomes, C ; Meester-Smoor, MA ; Richardson, AJ ; Mitchell, PA ; Taylor, KD ; Melles, RB ; Aldave, AJ ; Mills, RA ; Cao, K ; Chan, E ; Daniell, MD ; Wang, JJ ; Rotter, JI ; Hewitt, AW ; MacGregor, S ; Klaver, CCW ; Ramdas, WD ; Craig, JE ; Iyengar, SK ; O'Brart, D ; Jorgenson, E ; Baird, PN ; Rabinowitz, YS ; Burdon, KP ; Hammond, CJ ; Tuft, SJ ; Hysi, PG (NATURE PORTFOLIO, 2021-03-01)
    Keratoconus is characterised by reduced rigidity of the cornea with distortion and focal thinning that causes blurred vision, however, the pathogenetic mechanisms are unknown. It can lead to severe visual morbidity in children and young adults and is a common indication for corneal transplantation worldwide. Here we report the first large scale genome-wide association study of keratoconus including 4,669 cases and 116,547 controls. We have identified significant association with 36 genomic loci that, for the first time, implicate both dysregulation of corneal collagen matrix integrity and cell differentiation pathways as primary disease-causing mechanisms. The results also suggest pleiotropy, with some disease mechanisms shared with other corneal diseases, such as Fuchs endothelial corneal dystrophy. The common variants associated with keratoconus explain 12.5% of the genetic variance, which shows potential for the future development of a diagnostic test to detect susceptibility to disease.
  • Item
    Thumbnail Image
    Genome-wide association meta-analysis of corneal curvature identifies novel loci and shared genetic influences across axial length and refractive error
    Fan, Q ; Pozarickij, A ; Tan, NYQ ; Guo, X ; Verhoeven, VJM ; Vitart, V ; Guggenheim, JA ; Miyake, M ; Tideman, JWL ; Khawaja, AP ; Zhang, L ; MacGregor, S ; Hoehn, R ; Chen, P ; Biino, G ; Wedenoja, J ; Saffari, SE ; Tedja, MS ; Xie, J ; Lanca, C ; Wang, YX ; Sahebjada, S ; Mazur, J ; Mirshahi, A ; Martin, NG ; Yazar, S ; Pennell, CE ; Yap, M ; Haarman, AEG ; Enthoven, CA ; Polling, J ; Hewitt, AW ; Jaddoe, VWV ; van Duijn, CM ; Hayward, C ; Polasek, O ; Tai, E-S ; Yoshikatsu, H ; Hysi, PG ; Young, TL ; Tsujikawa, A ; Wang, JJ ; Mitchell, P ; Pfeiffer, N ; Parssinen, O ; Foster, PJ ; Fossarello, M ; Yip, SP ; Williams, C ; Hammond, CJ ; Jonas, JB ; He, M ; Mackey, DA ; Wong, T-Y ; Klaver, CCW ; Saw, S-M ; Baird, PN ; Cheng, C-Y (NATURE PORTFOLIO, 2020-03-19)
    Corneal curvature, a highly heritable trait, is a key clinical endophenotype for myopia - a major cause of visual impairment and blindness in the world. Here we present a trans-ethnic meta-analysis of corneal curvature GWAS in 44,042 individuals of Caucasian and Asian with replication in 88,218 UK Biobank data. We identified 47 loci (of which 26 are novel), with population-specific signals as well as shared signals across ethnicities. Some identified variants showed precise scaling in corneal curvature and eye elongation (i.e. axial length) to maintain eyes in emmetropia (i.e. HDAC11/FBLN2 rs2630445, RBP3 rs11204213); others exhibited association with myopia with little pleiotropic effects on eye elongation. Implicated genes are involved in extracellular matrix organization, developmental process for body and eye, connective tissue cartilage and glycosylation protein activities. Our study provides insights into population-specific novel genes for corneal curvature, and their pleiotropic effect in regulating eye size or conferring susceptibility to myopia.