Journal
HUMAN MOLECULAR GENETICS
Volume 21, Issue 18, Pages 4138-4150Publisher
OXFORD UNIV PRESS
DOI: 10.1093/hmg/dds225
Keywords
-
Funding
- Medical Research Council, UK [G0000067]
- Macular Disease Society
- Guide Dogs for the Blind Association [OR2006-02d]
- Fight for Sight
- Wellcome Trust [061860, 091388, 061858, 091157]
- Juvenile Diabetes Research Foundation [4-2000-948, 9-2005-25, 9-2011-253]
- Giles' Family Memorial Funds
- Macula Vision Research Foundation
- Chief Scientist Office, Scotland [CZB/4/79]
- Brian Mercer Charitable Trust
- British Council for the Prevention of Blindness
- TFC Frost Charitable Trust
- Gift of Sight
- Centre National de Genotypage
- Inserm (Centre d'Investigation Clinique des Quinze-Vingts)
- Department of Health's NIHR Biomedical Research Centre for Ophthalmology at Moorfields Eye Hospital
- UCL Institute of Ophthalmology
- Manchester NIHR Biomedical Research Centre
- MRC [G0000067, MC_U127527198, MC_PC_U127527198, G0000934, MC_U127584475] Funding Source: UKRI
- Cancer Research UK [12076] Funding Source: researchfish
- Chief Scientist Office [CZB/4/505, ETM/55, CZB/4/449] Funding Source: researchfish
- Medical Research Council [MC_PC_U127527198, G0000934, MC_PC_U127584475, G0000067, G0700704B, MC_U127584475, MC_U127527198] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0507-10094] Funding Source: researchfish
Ask authors/readers for more resources
Age-related macular degeneration (AMD) is a leading cause of visual loss in Western populations. Susceptibility is influenced by age, environmental and genetic factors. Known genetic risk loci do not account for all the heritability. We therefore carried out a genome-wide association study of AMD in the UK population with 893 cases of advanced AMD and 2199 controls. This showed an association with the well-established AMD risk loci ARMS2 (age-related maculopathy susceptibility 2)HTRA1 (HtrA serine peptidase 1) (P 2.7 10(72)), CFH (complement factor H) (P 2.3 10(47)), C2 (complement component 2)CFB (complement factor B) (P 5.2 10(9)), C3 (complement component 3) (P 2.2 10(3)) and CFI (P 3.6 10(3)) and with more recently reported risk loci at VEGFA (P 1.2 10(3)) and LIPC (hepatic lipase) (P 0.04). Using a replication sample of 1411 advanced AMD cases and 1431 examined controls, we confirmed a novel association between AMD and single-nucleotide polymorphisms on chromosome 6p21.3 at TNXB (tenascin XB)FKBPL (FK506 binding protein like) [rs12153855/rs9391734; discovery P 4.3 10(7), replication P 3.0 10(4), combined P 1.3 10(9), odds ratio (OR) 1.4, 95 confidence interval (CI) 1.31.6] and the neighbouring gene NOTCH4 (Notch 4) (rs2071277; discovery P 3.2 10(8), replication P 3.8 10(5), combined P 2.0 10(11), OR 1.3, 95 CI 1.21.4). These associations remained significant in conditional analyses which included the adjacent C2CFB locus. TNXB, FKBPL and NOTCH4 are all plausible AMD susceptibility genes, but further research will be needed to identify the causal variants and determine whether any of these genes are involved in the pathogenesis of AMD.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available