ArticleHuman genomics2021
Protective chromosome 1q32 haplotypes mitigate risk for age-related macular degeneration associated with the CFH-CFHR5 and ARMS2/HTRA1 loci.
Article in Human genomics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 35 citations in OpenAlex.
- Association of Complement Genetics with Outcomes in IgA Nephropathy.Clinical journal of the American Society of Nephrology : CJASN · 2026Article
- Carotenoid Status and Psychological Impact of Presymptomatic Macular Degeneration Genetic Risk Assessment: The MAGENTA Randomized Trial.Ophthalmology science · 2026Article
- TheOphthalmology science · 2026Article
- Truncated complement factor H Y402 gene therapy rescues C3 glomerulonephritis.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Alzheimer's disease and age-related macular degeneration: Shared and distinct immune mechanisms.Immunity · 2025Review
- Dissecting the biological complexity of age-related macular degeneration: Is it one disease, multiple separate diseases, or a spectrum?Experimental eye research · 2025Review
- Role of Oxidative Stress and Inflammation in Age Related Macular Degeneration: Insights into the Retinal Pigment Epithelium (RPE).International journal of molecular sciences · 2025Review
- The AMD-associated genetic polymorphism CFH Y402H confers vulnerability to Hydroquinone-induced stress in iPSC-RPE cells.Frontiers in immunology · 2025Article
- Genome-wide association analyses identify distinct genetic architectures for age-related macular degeneration across ancestries.Nature genetics · 2024Article
- The AKT2/SIRT5/TFEB pathway as a potential therapeutic target in non-neovascular AMD.Nature communications · 2024Article
- Challenges and opportunities of developing small-molecule therapies for age-related macular degeneration.Archives of pharmacal research · 2024Review
- Modeling complex age-related eye disease.Progress in retinal and eye research · 2024Review
- Levels of the HtrA1 Protein in Serum and Vitreous Humor Are Independent of Genetic Risk for Age-Related Macular Degeneration at the 10q26 Locus.Investigative ophthalmology & visual science · 2024Article
- Levels of complement factor H-related 4 protein do not influence susceptibility to age-related macular degeneration or its course of progression.Nature communications · 2024Article
- Geographic Atrophy in Age-Related Macular Degeneration: A Tale of Two Stages.Ophthalmology science · 2023Article
- AAV Gene Augmentation of Truncated Complement Factor H Differentially Rescues Ocular Complement Dysregulation in a Mouse Model.Investigative ophthalmology & visual science · 2023Article
- Article
- Genetic Variability of Complement Factor H Has Ethnicity-Specific Associations With Choroidal Thickness.Investigative ophthalmology & visual science · 2023Article
- Genetic variability shapes the alternative pathway complement activity and predisposition to complement-related diseases.Immunological reviews · 2023Review
- Systems genomics in age-related macular degeneration.Experimental eye research · 2022Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
backgroundSingle-variant associations with age-related macular degeneration (AMD), one of the most prevalent causes of irreversible vision loss worldwide, have been studied extensively. However, because of a lack of refinement of these associations, there remains considerable ambiguity regarding what constitutes genetic risk and/or protection for this disease, and how genetic combinations affect this risk. In this study, we consider the two most common and strongly AMD-associated loci, the CFH-CFHR5 region on chromosome 1q32 (Chr1 locus) and ARMS2/HTRA1 gene on chromosome 10q26 (Chr10 locus).
resultsBy refining associations within the CFH-CFHR5 locus, we show that all genetic protection against the development of AMD in this region is described by the combination of the amino acid-altering variant CFH I62V (rs800292) and genetic deletion of CFHR3/1. Haplotypes based on CFH I62V, a CFHR3/1 deletion tagging SNP and the risk variant CFH Y402H are associated with either risk, protection or neutrality for AMD and capture more than 99% of control- and case-associated chromosomes. We find that genetic combinations of CFH-CFHR5 haplotypes (diplotypes) strongly influence AMD susceptibility and that individuals with risk/protective diplotypes are substantially protected against the development of disease. Finally, we demonstrate that AMD risk in the ARMS2/HTRA1 locus is also mitigated by combinations of CFH-CFHR5 haplotypes, with Chr10 risk variants essentially neutralized by protective CFH-CFHR5 haplotypes.
conclusionsOur study highlights the importance of considering protective CFH-CFHR5 haplotypes when assessing genetic susceptibility for AMD. It establishes a framework that describes the full spectrum of AMD susceptibility using an optimal set of single-nucleotide polymorphisms with known functional consequences. It also indicates that protective or preventive complement-directed therapies targeting AMD driven by CFH-CFHR5 risk haplotypes may also be effective when AMD is driven by ARMS2/HTRA1 risk variants.
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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.