ArticleHuman molecular genetics2015
Rare genetic variants in the CFI gene are associated with advanced age-related macular degeneration and commonly result in reduced serum factor I levels.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 1 of them a synthesis that pooled it.
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Who cites it
75 citing papers in PubMed, 1 synthesis or guideline pooled it, 126 citations in OpenAlex.
- 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
- Mapping rare, deleterious mutations in Factor H: Association with early onset, drusen burden, and lower antigenic levels in familial AMD.Scientific reports · 2016Trial
- 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
- 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
- Epigenetic Alterations in Age-Related Macular Degeneration: Mechanisms and Implications.International journal of molecular sciences · 2025Review
- Enhanced retinal pigment epithelial cells as a delivery vehicle for retinal disease.Molecular therapy. Methods & clinical development · 2025Article
- The role of complement factor I rare genetic variants in age related macular degeneration in Finland.Human molecular genetics · 2025Article
- C3 glomerulopathy is highly prevalent in French Polynesia.Journal of translational autoimmunity · 2024Article
- Comprehensive functional characterization of complement factor I rare variant genotypes identified in the SCOPE geographic atrophy cohort.The Journal of biological chemistry · 2024Article
- Whole genome sequencing of 4,787 individuals identifies gene-based rare variants in age-related macular degeneration.Human molecular genetics · 2024Article
- The Lectin Pathway of the Complement System-Activation, Regulation, Disease Connections and Interplay with Other (Proteolytic) Systems.International journal of molecular sciences · 2024Review
- Recent Advances in Our Understanding of Age-Related Macular Degeneration: Mitochondrial Dysfunction, Redox Signaling, and the Complement System.Aging and disease · 2024Review
- Article
- Functional evaluation of rare variants in complement factor I using a minigene assay.Frontiers in immunology · 2024Article
- Complement Factor I Gene Variant as a Treatable Cause of Recurrent Aseptic Neutrophilic Meningitis: A Case Report.Neurology(R) neuroimmunology & neuroinflammation · 2023Article
- Rare DysfunctionalOphthalmology science · 2023Article
- Bruch's Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration.Journal of clinical medicine · 2023Review
- Identifying Novel Genes and Variants in Immune and Coagulation Pathways Associated with Macular Degeneration.Ophthalmology science · 2023Article
- Functional evaluation of complement factor I variants by immunoassays and SDS-PAGE.Frontiers in immunology · 2023Article
15 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 6 institutions in 2 countries.
Funding
Abstract
To assess a potential diagnostic and therapeutic biomarker for age-related macular degeneration (AMD), we sequenced the complement factor I gene (CFI) in 2266 individuals with AMD and 1400 without, identifying 231 individuals with rare genetic variants. We evaluated the functional impact by measuring circulating serum factor I (FI) protein levels in individuals with and without rare CFI variants. The burden of very rare (frequency <1/1000) variants in CFI was strongly associated with disease (P = 1.1 × 10(-8)). In addition, we examined eight coding variants with counts ≥5 and saw evidence for association with AMD in three variants. Individuals with advanced AMD carrying a rare CFI variant had lower mean FI compared with non-AMD subjects carrying a variant (P < 0.001). Further new evidence that FI levels drive AMD risk comes from analyses showing individuals with a CFI rare variant and low FI were more likely to have advanced AMD (P = 5.6 × 10(-5)). Controlling for covariates, low FI increased the risk of advanced AMD among those with a variant compared with individuals without advanced AMD with a rare CFI variant (OR 13.6, P = 1.6 × 10(-4)), and also compared with control individuals without a rare CFI variant (OR 19.0, P = 1.1 × 10(-5)). Thus, low FI levels are strongly associated with rare CFI variants and AMD. Enhancing FI activity may be therapeutic and measuring FI provides a screening tool for identifying patients who are most likely to benefit from complement inhibitory therapy.
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