ArticleJournal of neuroinflammation2016
Multiallelic copy number variation in the complement component 4A (C4A) gene is associated with late-stage age-related macular degeneration (AMD).
Article in Journal of neuroinflammation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 28 citations in OpenAlex.
- Association of Rare Predicted Loss-of-Function Variants in Cellular Pathways with Sub-Phenotypes in Age-Related Macular Degeneration.Ophthalmology · 2018Trial
- Cardiovascular peptide markers are associated with age-related macular degeneration in the Bialystok PLUS general population cohort.Scientific reports · 2026Article
- 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
- The Relationship between Complements and Age-Related Macular Degeneration and Its Pathogenesis.Journal of ophthalmology · 2024Review
- Risk and protection of different rare protein-coding variants of complement component C4A in age-related macular degeneration.Frontiers in genetics · 2023Article
- Predicting late-stage age-related macular degeneration by integrating marginally weak SNPs in GWA studies.Frontiers in genetics · 2023Article
- Circulating inflammatory monocytes oppose microglia and contribute to cone cell death in retinitis pigmentosa.PNAS nexus · 2022Article
- Semi-Quantitative Multiplex Profiling of the Complement System Identifies Associations of Complement Proteins with Genetic Variants and Metabolites in Age-Related Macular Degeneration.Journal of personalized medicine · 2021Article
- Genome Scan for Variable Genes Involved in Environmental Adaptations of Nubian Ibex.Journal of molecular evolution · 2021Article
- The complement system in age-related macular degeneration.Cellular and molecular life sciences : CMLS · 2021Review
- Novel Possible Protein Targets in Neovascular Age-Related Macular Degeneration: A Pilot Study Experiment.Frontiers in medicine · 2021Article
- Age-Related Macular Degeneration: Epidemiology and Clinical Aspects.Advances in experimental medicine and biology · 2021Article
- Complement C4 Gene Copy Number Variation Genotyping by High Resolution Melting PCR.International journal of molecular sciences · 2020Article
- Plasma biomarkers of the amyloid pathway are associated with geographic atrophy secondary to age-related macular degeneration.PloS one · 2020Article
- Cell-Type-Specific Complement Expression in the Healthy and Diseased Retina.Cell reports · 2019Article
- Genetic Basis of Phenotypic Differences Between Chinese Yunling Black Goats and Nubian Goats Revealed by Allele-Specific Expression in Their F1 Hybrids.Frontiers in genetics · 2019Article
- Y chromosome mosaicism is associated with age-related macular degeneration.European journal of human genetics : EJHG · 2019Article
- A mega-analysis of expression quantitative trait loci (eQTL) provides insight into the regulatory architecture of gene expression variation in liver.Scientific reports · 2018Article
- Major review: Molecular genetics of primary open-angle glaucoma.Experimental eye research · 2017Review
- Genetic pleiotropy between age-related macular degeneration and 16 complex diseases and traits.Genome medicine · 2017Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
Abstract
backgroundAge-related macular degeneration (AMD) is the leading cause of vision loss in Western societies with a strong genetic component. Candidate gene studies as well as genome-wide association studies strongly implicated genetic variations in complement genes to be involved in disease risk. So far, no association of AMD with complement component 4 (C4) was reported probably due to the complex nature of the C4 locus on chromosome 6.
methodsWe used multiplex ligation-dependent probe amplification (MLPA) to determine the copy number of the C4 gene as well as of both relevant isoforms, C4A and C4B, and assessed their association with AMD using logistic regression models.
resultsHere, we report on the analysis of 2645 individuals (1536 probands and 1109 unaffected controls), across three different centers, for multiallelic copy number variation (CNV) at the C4 locus. We find strong statistical significance for association of increased copy number of C4A (OR 0.81 (0.73; 0.89);P = 4.4 × 10(-5)), with the effect most pronounced in individuals over 78 years (OR 0.67 (0.55; 0.81)) and females (OR 0.77 (0.68; 0.87)). Furthermore, this association is independent of known AMD-associated risk variants in the nearby CFB/C2 locus, particularly in females and in individuals over 78 years.
conclusionsOur data strengthen the notion that complement dysregulation plays a crucial role in AMD etiology, an important finding for early intervention strategies and future therapeutics. In addition, for the first time, we provide evidence that multiallelic CNVs are associated with AMD pathology.
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