Evidence map›Paper›PMID 35693873›Full record

ArticleOphthalmology science2022

Evaluating a Causal Relationship between Complement Factor I Protein Level and Advanced Age-Related Macular Degeneration Using Mendelian Randomization.

Amy V Jones, Stuart MacGregor, Xikun Han, James Francis, Claire Harris, SCOPE Study group, David Kavanagh, Andrew Lotery, Nadia Waheed

Open access · goldAbstract read
In one paragraph

Article in Ophthalmology science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
3.3field-weighted citation impact, top 8% 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

8 citing papers in PubMed, 16 citations in OpenAlex.

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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 6 institutions in 4 countries.

Amy V JonesGyroscope Therapeutics Ltd, London, UK.
Stuart MacGregorStatistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Xikun HanStatistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
James FrancisGyroscope Therapeutics Ltd, London, UK.
Claire HarrisGyroscope Therapeutics Ltd, London, UK.
SCOPE Study group
David KavanaghClinical & Translational Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Andrew LoteryClinical Neurosciences, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
Nadia WaheedGyroscope Therapeutics Ltd, London, UK.
ManRos Therapeutics (France) · FRQIMR Berghofer Medical Research Institute · AURoyal Victoria Infirmary · GBThe University of Queensland · AUTufts University · USUniversity Hospital Southampton NHS Foundation Trust · GB

Funding

Statistical MethodsP01CA087969 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI ROSNER, BERNARD A · 2000 to 2019
$77.8M
University of Wisconsin Institute for Clinical and Translational ResearchUL1TR002373 · NCATS · UNIVERSITY OF WISCONSIN-MADISON · PI ELIZABETH S BURNSIDE, Allan R. Brasier · 2017 to 2026
$75.9M
Institutional Clinical and Translational Science AwardUL1TR000427 · NCATS · UNIVERSITY OF WISCONSIN-MADISON · PI DREZNER, MARC KENNETH · 2012 to 2016
$32.2M
Proteomics CoreP30EY010572 · NEI · OREGON HEALTH & SCIENCE UNIVERSITY · PI Kate E Keller · 1995 to 2026
$19.4M
VISION RESEARCHP30EY005722 · NEI · DUKE UNIVERSITY · PI Vadim Y Arshavsky · 1985 to 2026
$19.3M
THE EPIDEMIOLOGY OF AGE-RELATED OCULAR DISEASEU10EY006594 · NEI · UNIVERSITY OF WISCONSIN-MADISON · PI GANGNON, RONALD E · 1987 to 2018
$17.3M
Baylor-Johns Hopkins Center for Mendelian GeneticsU54HG006542 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI VALLE, DAVID · 2012 to 2015
$15.6M
Dietary Etiology of Heart DiseaseR01HL035464 · NHLBI · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI ERIC B RIMM, Qi Sun · 1986 to 2026
$13.6M
Instrumentation, Fabrication, and Design CoreP30EY019007 · NEI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Xin Zhang · 2010 to 2026
$12.9M
Unifying Genetics Epidemiology of Macular DegenerationR01EY012118 · NEI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI AGARWAL, ANITA, HAINES, JONATHAN L · 2006 to 2015
$12.2M
Shared Equipment ModuleP30EY014801 · NEI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI Dmitry V Ivanov · 2004 to 2026
$12.2M
GENETICS OF AGE-RELATED MACULOPATHYR01EY009859 · NEI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GORIN, MICHAEL B · 1993 to 2011
$11.5M
Intramural NIH HHS ZIA EY000475Medical Research Council G0000067NCATS NIH HHS UL1 TR000427NCATS NIH HHS UL1 TR002373NCI NIH HHS P01 CA087969NCI NIH HHS R01 CA049449NCI NIH HHS U01 CA049449NEI NIH HHS P30 EY005722NEI NIH HHS P30 EY010572NEI NIH HHS P30 EY014801NEI NIH HHS P30 EY019007NEI NIH HHS P30 EY022589NEI NIH HHS R01 EY009611NEI NIH HHS R01 EY009859NEI NIH HHS R01 EY012118NEI NIH HHS R01 EY013435NEI NIH HHS R01 EY014428NEI NIH HHS R01 EY016862NEI NIH HHS R01 EY017362NEI NIH HHS R01 EY018660NEI NIH HHS R01 EY021532NEI NIH HHS R01 EY021900NEI NIH HHS R01 EY022005NEI NIH HHS R01 EY022310NEI NIH HHS R01 EY023164NEI NIH HHS R03 EY013824NEI NIH HHS T32 EY007157NEI NIH HHS T32 EY023194NEI NIH HHS U10 EY006594NEI NIH HHS U10 EY012118NHGRI NIH HHS R01 HG007022NHGRI NIH HHS U01 HG006389NHGRI NIH HHS U01 HG006513NHGRI NIH HHS U54 HG006542NHLBI NIH HHS R01 HL035464NIA NIH HHS F31 AG044089NIA NIH HHS R01 AG019085Wellcome Trust
6 · The paper itself

Abstract

Importance: Risk of advanced age-related macular degeneration (AAMD) is associated with rare genetic variants in the gene encoding Complement factor I ( Objective: Can genetic factors be used to infer whether low circulating CFI is associated with AAMD risk? Design: Two-sample inverse variance weighted Mendelian Randomisation (MR) was used to evaluate evidence for a relationship between CFI levels and AAMD risk, comparing CFI levels from genetically predefined subsets in AAMD and control cohorts. Setting: Published genetic and proteomic data was combined with data from cohorts of Geographic Atrophy (GA) patients in a series of MR analyses. Participants: We derived genetic instruments for systemic CFI level in 3,301 healthy European participants in the INTERVAL study. To evaluate a genetic causal odds ratio (OR) for the effect of CFI levels on AAMD risk, we used results from a genome-wide association study of 12,711 AAMD cases and 14,590 European controls from the International AMD Genomics Consortium (IAMDGC), and CFI levels from patients entered into the research studies SCOPE and SIGHT. Results: We identified one common Conclusion and relevance: Excellent concordance in direction and effect size derived from rare and common variant calculations provide good genetic evidence for a potentially causal role of lower CFI level increasing AAMD risk.

Indexed as

Advanced age-related macular degenerationbiomarkersCFIFactor Igenetics

Identifiers

PMID35693873
PMCPMC9186402
OpenAlexW4221110422

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.