Trial reportOphthalmology2018
Association of Rare Predicted Loss-of-Function Variants in Cellular Pathways with Sub-Phenotypes in Age-Related Macular Degeneration.
Trial report in Ophthalmology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
8 citing papers in PubMed, 15 citations in OpenAlex.
- 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
- Comparative study on genomic and epigenomic profiles of retinoblastoma or tuberous sclerosis complex via nanopore sequencing and a joint screening framework.Cancer gene therapy · 2024Article
- Whole genome sequencing of 4,787 individuals identifies gene-based rare variants in age-related macular degeneration.Human molecular genetics · 2024Article
- Whole Genome Sequencing Identifies Novel Common and Low-Frequency Variants Associated With Age-Related Macular Degeneration.Investigative ophthalmology & visual science · 2023Article
- Symmetry of Macular Fundus Features in Age-Related Macular Degeneration.Ophthalmology. Retina · 2023Article
- Making Biological Sense of Genetic Studies of Age-Related Macular Degeneration.Advances in experimental medicine and biology · 2021Article
- Family-based exome sequencing identifies rare coding variants in age-related macular degeneration.Human molecular genetics · 2020Article
- Association of age-related macular degeneration with complement activation products, smoking, and single nucleotide polymorphisms in South Carolinians of European and African descent.Molecular vision · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
purposeTo investigate the association of rare predicted loss-of-function (pLoF) variants within age-related macular degeneration (AMD) risk loci and AMD sub-phenotypes.
designCase-control study.
participantsParticipants of AREDS, AREDS2, and Michigan Genomics Initiative.
methodsWhole genome sequencing data were analyzed for rare pLoF variants (frequency <0.1%) in the regions of previously identified 52 independent risk variants known to be associated with AMD. Frequency of the rare pLoF variants in cases with intermediate or advanced AMD was compared with controls. Variants were assigned to the complement, extracellular matrix (ECM), lipid, cell survival, immune system, metabolism, or unknown/other pathway. Associations of rare pLoF variant pathways with AMD sub-phenotypes were analyzed using logistic and linear regression, and Cox proportional hazards models.
main outcome measuresDifferences in rare pLoF variant pathway burden and association of rare pLoF variant pathways with sub-phenotypes within the population with AMD were evaluated.
resultsRare pLoF variants were found in 298 of 1689 cases (17.6%) and 237 of 1518 controls (15.6%) (odds ratio [OR], 1.11; 95% confidence interval [CI], 0.91-1.36; P = 0.310). An enrichment of rare pLoF variants in the complement pathway in cases versus controls (OR, 2.94; 95% CI, 1.49-5.79; P = 0.002) was observed. Within cases, associations between all rare pLoF variants and choroidal neovascularization (CNV) (OR, 1.34; 95% CI, 1.04-1.73; P = 0.023), calcified drusen (OR, 1.33; 95% CI, 1.04-1.72; P = 0.025), higher scores on the AREDS Extended AMD Severity Scale (Standardized Coefficient Beta (β)=0.346 [0.086-0.605], P = 0.009), and progression to advanced disease (hazard ratio, 1.25; 95% CI, 1.01-1.55; P = 0.042) were observed. At the pathway level, there were associations between the complement pathway and geographic atrophy (GA) (OR, 2.17; 95% CI, 1.12-4.24; P = 0.023), the complement pathway and calcified drusen (OR, 3.75; 95% CI, 1.79-7.86; P < 0.001), and the ECM pathway and more severe levels in the AREDS Extended AMD Severity Scale (β = 0.62; 95% CI, 0.04-1.20; P = 0.035).
conclusionsRare pLoF variants are associated with disease progression. Variants in the complement pathway modify the clinical course of AMD and increase the risk of developing specific sub-phenotypes.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.