| Title: |
Association of Novel Loci With Keratoconus Susceptibility in a Multitrait Genome-Wide Association Study of the UK Biobank Database and Canadian Longitudinal Study on Aging |
| Authors: |
He, W; Han, X; Ong, JS; Hewitt, AW; MacKey, DA; Gharahkhani, P; MacGregor, S; Aung, T; Burdon, KP; Cheng, CY; Craig, JE; Cree, AJ; Hammond, CJ; Höhn, R; Hysi, P; Iglesias Gonzalez, AI; Jonas, J; Khawaja, A; Khor, CC; Klaver, CCW; Pasutto, F; Mitchell, P; Mishra, A; Pang, C; Pasquale, LR; Springelkamp, H; Thorleifsson, G; Thorsteinsdottir, U; Van Duijn, CM; Viswanathan, A; Vitart, V; Wiggs, JL; Wojciechowski, R; Wong, T; Young, TL; Zeller, T |
| Source: |
JAMA Ophthalmology , 140 (6) pp. 568-576. (2022) |
| Publisher Information: |
American Medical Association (AMA) |
| Publication Year: |
2022 |
| Collection: |
University College London: UCL Discovery |
| Subject Terms: |
Aging; Biological Specimen Banks; Canada; Cornea; Female; Genome-Wide Association Study; Glaucoma; Humans; Keratoconus; Longitudinal Studies; Male; Middle Aged; United Kingdom; Young Adult |
| Description: |
Importance: Keratoconus can be a debilitating corneal ectasia in which the cornea thins, bulges, and steepens into a conical shape. Early features of keratoconus include myopia and irregular astigmatism, which affect vision and can be treated with contact lenses, collagen cross-linking, or, in advanced cases, corneal transplant. Recent estimates of the prevalence of keratoconus based on results of Scheimpflug imaging in young adults are as high as 1.2%. However, obtaining very large keratoconus data sets for a genome-wide association study (GWAS) is problematic because few population studies include Scheimpflug imaging and because severe keratoconus is relatively rare. Objective: To identify novel keratoconus loci using corneal resistance factor (CRF) and central corneal thickness (CCT). Design, Setting, and Participants: This multitrait GWAS used European ancestry CRF data from UK Biobank (UKB) (n = 105 427) and the Canadian Longitudinal Study on Aging (CLSA) (n = 18307) and European ancestry CCT data from the International Glaucoma Genetics Consortium (IGGC) (n = 17803). The CRF and CCT variants in published keratoconus data sets (4669 cases and 116547 controls) were compared. The data set from UKB was compiled March 24, 2020; data were released from the CLSA in July 2020; and IGGC data were available from May 1, 2018. Main Outcomes and Measures: Association of CRF and CCT variants with keratoconus risk. Results: The GWAS included 4 cohorts: 105427 UKB European ancestry (56 134 women [53.2%] and 49 293 men [46.7%]; mean [SD] age, 57 [8] years), 5029 UKB South Asian ancestry (2368 women [47.1%] and 2661 men [52.9%]; mean [SD] age, 54 [8] years), 902 UKB East Asian ancestry (622 women [68.9%] and 280 men [31.0%]; mean [SD] age, 53 [8] years), and 18307 CLSA European ancestry (9260 women [50.6%] and 9047 men [49.4%]; mean [SD] age, 63 [10] years) participants. A total of 369 CRF and 233 CCT loci were identified, including 36 novel CRF loci and 114 novel CCT loci. Twenty-nine CRF loci and 24 CCT loci were ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
https://discovery.ucl.ac.uk/id/eprint/10151779/ |
| Availability: |
https://discovery.ucl.ac.uk/id/eprint/10151779/ |
| Accession Number: |
edsbas.D60FB4FD |
| Database: |
BASE |