期刊
COMMUNICATIONS BIOLOGY
卷 4, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s42003-021-01784-0
关键词
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资金
- Moorfields Eye Charity
- Wellcome Trust medical charity, Medical Research Council, Department of Health, Scottish Government
- Northwest Regional Development Agency
- Welsh Assembly Government
- British Heart Foundation
- Diabetes UK
- Moorfields, London, UK - Moorfields Eye Charity
- Rosetrees Trust
- National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital
- UCL Institute of Ophthalmology
- UK Research and Innovation Future Leadership Fellowship
- Academy of Medical Sciences Springboard award
- HighThroughput Genomics Group at the Wellcome Trust Centre for Human Genetics - Wellcome Trust [203141/Z/16/Z]
- Moorfields Eye Charity Career Development Fellowships
- GERA, USA
- Robert Wood Johnson Foundation
- Gladys Valley Foundation
- Ellison Medical Foundation
- Kaiser Permanente Community Benefit Programs - National Institute on Aging, National Institute of Mental Health
- National Institute of Health Common Fund [RC2 AG036607]
- National Eye Institute (NEI) [R01 EY027004]
- National Institute of Diabetes and Digestive and Kidney Diseases [R01 DK116738]
- Eye Defects Research Foundation Inc.
- NEI [R01-09052]
- National Institutes of Health [U19 HL069757]
- National Heart, Lung, and Blood Institute [UL1TR000124]
- National Center for Advancing Translational Sciences
- National Institutes of Health, National Eye Institute [R01 EY009052]
- National Center for Advancing Translational Sciences, CTSI [UL1TR001881]
- National Health and Medical Research Council (NHMRC) [1104700]
- Centre for Research Excellence [1023911]
- AMD Genetics Consortium genotyped under The Center for Inherited Diseases Research (CIDR) Program [HHSN268201200008I]
- NHMRC Fellowship
- NHMRC [1150144, 1116360]
- NHMRC Senior Research Fellowship [1059954]
- King's College London
- Fight for Sight PhD studentship
- Fight for Sight ECI fellowship
- KCL Department of Ophthalmology [669, 17615]
- Leeds University and Leeds Teaching Hospitals NHS Trust [SAC007, SAC033]
- National Eye Research Centre
- Fight For Sight
- MRC [408757]
- University of Melbourne, Royal Victorian Eye and Ear Hospital, Australia
- Australian National Health and Medical Research Council (NHMRC) [1104700, 1138585]
- Angior Family Foundation
- Lions Eye Foundation Fellowship
- Victorian Government
- Charles University and General University Hospital in Prague, Czech Republic [UNCE/MED/007, PROGRES1086, Q26/LF1]
- Charles University [GACR 20-19278S]
- Erasmus Medical Center
- Combined Ophthalmic Research Rotterdam (CORR) grant
- National Health and Medical Research Council of Australia [1150144, 1116360, 1104700, 1059954] Funding Source: NHMRC
- MRC [G1002002] Funding Source: UKRI
- UKRI [MR/S031820/1] Funding Source: UKRI
The study provides insights into the genetic basis of keratoconus, identifying multiple genomic loci associated with the disease and implicating genetic pathways related to collagen matrix integrity and cell differentiation. This has potential implications for future diagnostic tests and treatments.
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. Alison Hardcastle et al. report a genome-wide meta-analysis of keratoconus, a condition affecting the cornea that causes blurred vision and often leads to blindness. They identify 36 genomic regions associated with keratoconus, 31 of which are novel, and show that the genes in these regions implicate genetic pathways involved in collagen matrix integrity and cell differentiation.
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