Evidence map›Paper›PMID 32516404›Full record

ArticleInvestigative ophthalmology & visual science2020

Rare Genetic Variants in Complement Factor I Lead to Low FI Plasma Levels Resulting in Increased Risk of Age-Related Macular Degeneration.

Thomas M Hallam, Kevin J Marchbank, Claire L Harris, Clive Osmond, Victoria G Shuttleworth, Helen Griffiths, Angela J Cree, David Kavanagh, Andrew J Lotery

Open access · goldAbstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Investigative ophthalmology & visual science, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
5.7field-weighted citation impact, top 3% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

33 citing papers in PubMed, 54 citations in OpenAlex.

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  15. Complement inhibitors for age-related macular degeneration.The Cochrane database of systematic reviews · 2023
    Review
  16. Rare DysfunctionalOphthalmology science · 2023
    Article
  17. Review
  18. Alternative pathway diagnostics.Immunological reviews · 2023
    Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 1 country.

Thomas M Hallam,.
Kevin J Marchbank,.
Claire L Harris,.
Clive Osmond,.
Victoria G Shuttleworth,.
Helen Griffiths,.
Angela J Cree,.
David Kavanagh,.
Andrew J Lotery,.
University of Southampton · GBNewcastle University · GBRoyal Victoria Infirmary · GB

Funding

Department of HealthMedical Research CouncilWellcome Trust
6 · The paper itself

Abstract

Purpose: Rare genetic variants in complement factor I (CFI) that cause low systemic levels of the protein (FI) have been reported as a strong risk factor for advanced age-related macular degeneration (AMD). This study set out to replicate these findings. Methods: FI levels were measured by sandwich ELISA in an independent cohort of 276 patients with AMD and 205 elderly controls. Single-nucleotide polymorphism genotyping and Sanger sequencing were used to assess genetic variability. Results: The median FI level was significantly lower in those individuals with AMD and a rare CFI variant (28.3 µg/mL) compared to those with AMD without a rare CFI variant (38.8 µg/mL, P = 0.004) or the control population with (41.7 µg/mL, P = 0.0085) or without (41.5 µg/mL, P < 0.0001) a rare CFI variant. Thirty-six percent of patients with AMD with a rare CFI variant had levels below the fifth percentile, compared to 6% in controls with CFI variants. Multiple regression analyses revealed a decreased FI level associated with a rare CFI variant was a risk factor for AMD (early or late AMD: odds ratio [OR] 12.05, P = 0.03; early AMD: OR 30.3, P = 0.02; late AMD: OR 10.64, P < 0.01). Additionally, measurement of FI in aqueous humor revealed a large FI concentration gradient between systemic circulation and the eye (∼286-fold). Conclusions: Rare genetic variants in CFI causing low systemic FI levels are strongly associated with AMD. The impermeability of the Bruch's membrane to FI will have implications for therapeutic replacement of FI in individuals with CFI variants and low FI levels at risk of AMD.

Indexed as

Genetic VariationPolymorphism, Single NucleotideAgedAged, 80 and overBiomarkersCase-Control StudiesComplement Factor HComplement Factor IEye ProteinsFemaleGenetic Predisposition to DiseaseGenetic TestingGenotyping TechniquesHumansMacular DegenerationMaleARMS2 protein, humanBiomarkersCFH protein, humanCFI protein, humanComplement Factor HComplement Factor IEye ProteinsProteinsReceptors, TNF-Related Apoptosis-Inducing LigandTNFRSF10A protein, humanVascular Endothelial Growth Factor AVEGFA protein, human

Identifiers

PMID32516404
PMCPMC7415286
OpenAlexW3034151544

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.