144363 - a multi ethnic genome wide.pdf (1.75 MB)
A multi-ethnic genome-wide association study implicates collagen matrix integrity and cell differentiation pathways in keratoconus
journal contributionposted on 2023-05-20, 23:20 authored by Hardcastle, AJ, Liskova, P, Bykhovskaya, Y, Bennet McComishBennet McComish, Davidson, AE, Inglehearn, CF, Li, X, Choquet, H, Habeeb, M, Sionne LucasSionne Lucas, Sahebjada, S, Pontikos, N, Lopez, KER, Khawaja, AP, Ali, M, Dudakova, L, Skalicka, P, Van Dooren, BTH, Geerards, AJM, Haudum, CW, Faro, VL, Tenen, A, Simcoe, MJ, Patasova, K, Yarrand, D, Yin, J, Siddiqui, S, Rice, A, Farraj, LA, Chen, YDI, Rahi, JS, Krauss, RM, Theusch, E, Jac CharlesworthJac Charlesworth, 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, Alexander HewittAlexander Hewitt, MacGregor, S, Klaver, CCW, Ramdas, WD, Jamie CraigJamie Craig, Iyengar, SK, O'Brart, D, Jorgenson, E, Baird, PN, Rabinowitz, YS, Kathryn BurdonKathryn Burdon, Hammond, CJ, Tuft, SJ, Hysi, PG
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.
Publication titleCommunications Biology
Department/SchoolMenzies Institute for Medical Research
PublisherNature Publishing Group UK
Place of publicationUnited Kingdom
Rights statement© The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, (http://creativecommons.org/ licenses/by/4.0/.) 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.