Variation near complement factor I is associated with risk of advanced AMD
Open accessAbstract
A case-control association study for advanced age-related macular degeneration was conducted to explore several regions of interest identified by linkage. This analysis identified a single nucleotide polymorphism just 3' of complement factor I on chromosome 4 showing significant association (P<10(-7)). Sequencing was performed on coding exons in linkage disequilibrium with the detected association. No obvious functional variation was discovered that could be the proximate cause of the association, suggesting a noncoding regulatory mechanism.
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Genes in the complement pathway and a region of chromosome 10 have been implicated as the major genetic contributors to AMD.
“Genes in the complement pathway4–11 and a region of chromosome 10 12,13 have now been implicated as the major genetic contributors to disease.”
From Seven new loci associated with age-related macular degeneration (2013) · cites this paper as [9]
Several additional complement genes have now been strongly associated with AMD, including complement 2 and/or complement factor B, complement 3, and complement factor I.
“These include complement 2 (C2) and/or complement factor B (CFB) (56), complement 3 (C3) (170), and complement factor I (CFI) (44).”
From Unraveling a Multifactorial Late-Onset Disease: From Genetic Susceptibility to Disease Mechanisms for Age-Related Macular Degeneration (2009) · cites this paper as [44]
The role of the alternative complement pathway in AMD pathogenesis was documented by the discovery and replication of the CFH association and by reports of three additional risk loci in this pathway: CFB/C2 on chromosome 6, C3 on chromosome 19, and CFI on chromosome 4.
“The role of the alternative complement pathway in disease pathogenesis was documented by the discovery ([2](#r2)–[5](#r5)) and replication ([6](#r6), [7](#r7)) of the *CFH* association as well as reports of three additional risk loci in this pathway: *CFB/C2* on chromosome 6 ([6](#r6), [8](#r8)), *C3* on chromosome 19 ([9](#r9), [10](#r10)), and *CFI* on chromosome 4 ([11](#r11)).”
From Genome-wide association study of advanced age-related macular degeneration identifies a role of the hepatic lipase gene ( <i>LIPC</i> ) (2010) · cites this paper as [11]
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“In addition to the two novel loci, 10 previously reported loci in ARMS2/HTRA1 (rs10490924), CFH (rs1061170, and rs1410996), CFB (rs641153), C3 (rs2230199), C2 (rs9332739), CFI (rs10033900), LIPC (rs10468017), TIMP3 (rs9621532) and CETP (rs3764261) were confirmed with genomewide significant signals in this large study.”
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- Authors
- Fagerness, J. A., Maller, J. B., Neale, B. M., Reynolds, R. C., Daly, M. J., & Seddon, J. M.
- Affiliations
- Massachusetts General Hospital (US)
- Broad Institute (US)
- Tufts Medical Center (US)
- Corresponding author
- Seddon, Johanna M
- Venue
- European Journal of Human Genetics
- Published
- 2008-08-06
- Volume
- 17
- Issue
- 1
- Pages
- 100-104
- ISSN
- 1018-4813 (ISSN-L)
- 1476-5438
- PMC
- PMC2985963
- OpenAlex
- W2092148373
- Cited by
- 357
- References
- 27
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 12 · 2023: 6 · 2022: 14 · 2021: 22 · 2020: 17 · 2019: 19 · 2018: 12 · 2017: 15 · 2016: 13 · 2015: 29 · 2014: 33 · 2013: 30 · 2012: 43
- FWCI
- 27.02
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- European Journal of Human Genetics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Foundation Fighting Blindness
- Research to Prevent Blindness
- Tufts Medical Center
- Broad Institute
- National Institutes of Health (6u54rr020278-06)
- National Eye Institute (U10EY011309, EY11309, R01EY011309)
- National Center for Research Resources (U54-RR020278)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Keywords
- advanced age-related macular degeneration, complement factor I, CFI, single nucleotide polymorphisms, genetic association, chromosome 4, linkage disequilibrium, genetic susceptibility
- MeSH terms
- Aged, Chromosomes, Human, Pair 4, Female, Humans, Macular Degeneration, Male, Middle Aged, Risk Factors, Linkage Disequilibrium, Case-Control Studies, Complement Factor I, Sequence Analysis, DNA, Risk Assessment, Polymorphism, Single Nucleotide
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