ArticleNature genetics2013
A functional variant in the CFI gene confers a high risk of age-related macular degeneration.
Article in Nature genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers, 2 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
119 citing papers in PubMed, 2 syntheses or guidelines pooled it, 186 citations in OpenAlex.
- Genetic determinants of age-related macular degeneration in Middle Eastern populations: a systematic review.Frontiers in genetics · 2026Pooled it
- Protective coding variants in CFH and PELI3 and a variant near CTRB1 are associated with age-related macular degeneration†.Human molecular genetics · 2016Pooled it
- Functional Analysis of Variants in Complement Factor I Identified in Age-Related Macular Degeneration and Atypical Hemolytic Uremic Syndrome.Frontiers in immunology · 2021Trial
- Trial
- Association of Rare Predicted Loss-of-Function Variants in Cellular Pathways with Sub-Phenotypes in Age-Related Macular Degeneration.Ophthalmology · 2018Trial
- Genetic evidence and cross-species functional characterization implicateProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Geographic Atrophy in Patients with Age-Related Macular Degeneration Is Associated with Rare Variants in Complement Factor H and Complement Factor I.Ophthalmology science · 2026Article
- Molecular Crosstalk in Age-Related Macular Degeneration: Integrating Oxidative Stress, Inflammation, microRNAs, and Genetic Susceptibility Toward Precision Therapeutics.Biomolecules · 2026Review
- Disease Progression in Age-Related Macular Degeneration Patients Carrying Rare Variants in the Complement Factor H or Complement Factor I Genes.Investigative ophthalmology & visual science · 2025Article
- Moss-derived human complement factor H modulates retinal immune response and attenuates retinal degeneration.Journal of neuroinflammation · 2025Article
- Decreased complement 4 and interleukin-10 as biomarkers in aqueous humour for non-exudative age-related macular degeneration: a case control study.Journal of translational medicine · 2025Article
- A cross-tissue transcriptome-wide association study identified susceptibility genes for age-related macular degeneration.Scientific reports · 2025Article
- The role of complement factor I rare genetic variants in age related macular degeneration in Finland.Human molecular genetics · 2025Article
- High prevalence of the hotspot complement factor I p.Ile357Met pathogenic variant in Tunisian atypical hemolytic uremic syndrome patients: report of three new cases and review of the literature.Frontiers in immunology · 2025Review
- Complement or insult: the emerging link between complement cascade deficiencies and pathology of myeloid malignancies.Journal of leukocyte biology · 2024Review
- Differential gene expression between central and peripheral retinal regions in dogs and comparison with humans.Experimental eye research · 2024Article
- Genetic Insights into Age-Related Macular Degeneration.Biomedicines · 2024Review
- Genetic and Epigenetic Biomarkers Linking Alzheimer's Disease and Age-Related Macular Degeneration.International journal of molecular sciences · 2024Review
- Comprehensive functional characterization of complement factor I rare variant genotypes identified in the SCOPE geographic atrophy cohort.The Journal of biological chemistry · 2024Article
- Functional evaluation of rare variants in complement factor I using a minigene assay.Frontiers in immunology · 2024Article
59 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
25 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Up to half of the heritability of age-related macular degeneration (AMD) is explained by common variants. Here, we report the identification of a rare, highly penetrant missense mutation in CFI encoding a p.Gly119Arg substitution that confers high risk of AMD (P = 3.79 × 10⁻⁶; odds ratio (OR) = 22.20, 95% confidence interval (CI) = 2.98-164.49). Plasma and sera from cases carrying the p.Gly119Arg substitution mediated the degradation of C3b, both in the fluid phase and on the cell surface, to a lesser extent than those from controls. Recombinant protein studies showed that the Gly119Arg mutant protein is both expressed and secreted at lower levels than wild-type protein. Consistent with these findings, human CFI mRNA encoding Arg119 had reduced activity compared to wild-type mRNA encoding Gly119 in regulating vessel thickness and branching in the zebrafish retina. Taken together, these findings demonstrate that rare, highly penetrant mutations contribute to the genetic burden of AMD.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.