A common CFH haplotype, with deletion of CFHR1 and CFHR3, is associated with lower risk of age-related macular degeneration
Open accessAbstract
Age-related macular degeneration (AMD; OMIM #603075) is the most frequent cause of visual impairment in the elderly population, with severe disease affecting nearly 10% of individuals of European descent over the age of 75 years. It is a complex disease in which genetic and environmental factors contribute to susceptibility. Complement factor H (CFH) has recently been identified as a major AMD susceptibility gene, and the Y402H polymorphism has been proposed as the likely causative factor. We genotyped polymorphisms spanning the cluster of CFH and five CFH-related genes on chromosome 1q23 in 173 individuals with severe neovascular AMD and 170 elderly controls with no signs of AMD. Detailed analysis showed a common haplotype associated with decreased risk of AMD that was present on 20% of chromosomes of controls and 8% of chromosomes of individuals with AMD. We found that this haplotype carried a deletion of CFHR1 and CFHR3, and the proteins encoded by these genes were absent in serum of homozygotes. The protective effect of the deletion haplotype cannot be attributed to linkage disequilibrium with Y402H and was replicated in an independent sample.
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Although a common deletion of CFHR1 and CFHR3 has been proposed, there was only modest signal in this study, likely due to linkage disequilibrium with the most significantly associated variants in the locus (r2=.31 between rs10737680 and 1000 Genomes Project MERGED_DEL_2_6731).
“Although a common deletion of the CFHR1 and CFHR3 genes has been proposed42,43, there was only modest signal in this study which is likely due to linkage disequilibrium with our most significantly associated variants in the locus (r2=.31 between rs10737680 and 1000 Genomes Project MERGED_DEL_2_6731) as previously suggested34.”
From Seven new loci associated with age-related macular degeneration (2013) · cites this paper as [42]
Deletions in two genes near CFH, CFHR1 and CFHR3, have been associated with reduced risk of AMD.
“In addition to simple sequence changes, deletions in two genes near CFH, CFHR1 and CFHR3, have been associated with reduced risk of AMD (75, 143) (see Figure 5).”
From Unraveling a Multifactorial Late-Onset Disease: From Genetic Susceptibility to Disease Mechanisms for Age-Related Macular Degeneration (2009) · cites this paper as [75]
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- Authors
- Hughes, A. E., Orr, N., Esfandiary, H., Diaz-Torres, M., Goodship, T., & Chakravarthy, U.
- Affiliations
- Queen's University Belfast (GB)
- Newcastle University (GB)
- Corresponding author
- Hughes, Anne E
- Venue
- Nature Genetics
- Published
- 2006-09-24
- Volume
- 38
- Issue
- 10
- Pages
- 1173-1177
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W1997761753
- Cited by
- 467
- References
- 16
- Citations by year
- 2026: 8 · 2025: 19 · 2024: 18 · 2023: 6 · 2022: 18 · 2021: 18 · 2020: 10 · 2019: 14 · 2018: 14 · 2017: 12 · 2016: 27 · 2015: 24 · 2014: 32 · 2013: 32 · 2012: 47
- FWCI
- 25.45
- Type
- journal article
- Language
- en
- Update notices
- erratum (2007-04-01)
- Open access
- green
- doi.org
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (Queen's University Belfast) (submittedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- age-related macular degeneration, complement factor H, neovascular AMD, genetic susceptibility, linkage disequilibrium, protective haplotypes
- MeSH terms
- Age Factors, Aged, Haplotypes, Humans, Macular Degeneration, Risk Factors, Case-Control Studies, Complement Factor H, Gene Deletion, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide
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