| Literature DB >> 33649486 |
Petra Liskova1,2,3, Yelena Bykhovskaya4,5, Bennet J McComish6, Alice E Davidson1, Chris F Inglehearn7, Alison J Hardcastle8,9, Xiaohui Li10, Hélène Choquet11, Mahmoud Habeeb12,13, Sionne E M Lucas6, Srujana Sahebjada14,15, Nikolas Pontikos1, Karla E Rojas Lopez1, Anthony P Khawaja1,16,17, Manir Ali7, Lubica Dudakova2, Pavlina Skalicka3, Bart T H Van Dooren12,18, Annette J M Geerards19, Christoph W Haudum20, Valeria Lo Faro21,22, Abi Tenen23,24,25, Mark J Simcoe26,27, Karina Patasova26,27, Darioush Yarrand27, Jie Yin11, Salina Siddiqui7,28, Aine Rice7, Layal Abi Farraj7, Yii-Der Ida Chen10, Jugnoo S Rahi29, Ronald M Krauss30, Elisabeth Theusch30, Jac C Charlesworth6, Loretta Szczotka-Flynn31, Carmel Toomes7, Magda A Meester-Smoor12,13, Andrea J Richardson14, Paul A Mitchell32, Kent D Taylor10, Ronald B Melles11, Anthony J Aldave33, Richard A Mills34, Ke Cao14,15, Elsie Chan14,15, Mark D Daniell14,15, Jie Jin Wang35, Jerome I Rotter10, Alex W Hewitt6,23,24,25, Stuart MacGregor36, Caroline C W Klaver12,13, Wishal D Ramdas12, Jamie E Craig6,34, Sudha K Iyengar31, David O'Brart26,37, Eric Jorgenson11, Paul N Baird15, Yaron S Rabinowitz4,5, Kathryn P Burdon6,34, Chris J Hammond26,27,37, Stephen J Tuft38,39, Pirro G Hysi40,41,42.
Abstract
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.Entities:
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Year: 2021 PMID： 33649486 PMCID： PMC7921564 DOI： 10.1038/s42003-021-01784-0
Source DB: PubMed Journal: Commun Biol ISSN： 2399-3642