Evidence map›Paper›PMID 22694956›Full record

ArticleHuman molecular genetics2012

Genome-wide association study of age-related macular degeneration identifies associated variants in the TNXB-FKBPL-NOTCH4 region of chromosome 6p21.3.

Valentina Cipriani, Hin-Tak Leung, Vincent Plagnol, Catey Bunce, Jane C Khan, Humma Shahid, Anthony T Moore, Simon P Harding, Paul N Bishop, Caroline Hayward and 24 more

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In one paragraph

Article in Human molecular genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed, 5 pooled it
9.6field-weighted citation impact, top 2% 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

54 citing papers in PubMed, 5 syntheses or guidelines pooled it, 90 citations in OpenAlex.

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  13. Immunogenetic and Environmental Factors in Age-Related Macular Disease.International journal of molecular sciences · 2024
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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

34 authors at 20 institutions in 4 countries.

Valentina CiprianiInstitute of Ophthalmology, University College London, London EC1V 9EL, UK. v.cipriani@ucl.ac.uk
Hin-Tak Leung
Vincent Plagnol
Catey Bunce
Jane C Khan
Humma Shahid
Anthony T Moore
Simon P Harding
Paul N Bishop
Caroline Hayward
Susan Campbell
Ana Maria Armbrecht
Baljean Dhillon
Ian J Deary
Harry Campbell
Malcolm Dunlop
Anna F Dominiczak
Samantha S Mann
Sharon A Jenkins
Andrew R Webster
Alan C Bird
Mark Lathrop
Diana Zelenika
Eric H Souied
José-Alain Sahel
Thierry Léveillard
French AMD Investigators
Angela J Cree
Jane Gibson
Sarah Ennis
Andrew J Lotery
Alan F Wright
David G Clayton
John R W Yates
University College London · GBMRC Institute of Genetics and Molecular Medicine · GBMoorfields Eye Hospital · GBUniversity of Cambridge · GBUniversity of Edinburgh · GBUniversity of Southampton · GBAddenbrooke's Hospital · GBChinese University of Hong Kong · CNFondation Jean Dausset-CEPH · FRHôpital Intercommunal de Créteil · FRInserm · FRMedical Research Council · GBPrincess Alexandra Eye Pavilion · GBSorbonne Université · FRSouthampton General Hospital · GBSt Thomas' Hospital · GBUniversity College Hospital · GBUniversity of Glasgow · GBUniversity of Liverpool · GBUniversity of Manchester · GB

Funding

Biotechnology and Biological Sciences Research CouncilCancer Research UK 12076Cancer Research UK A8896Cancer Research UK C3 48/A3758Cancer Research UK C48/A6361Chief Scientist Office CZB/4/449Chief Scientist Office CZB/4/505Chief Scientist Office ETM/55Medical Research Council G0000067Medical Research Council G0000657-53203Medical Research Council G0000934Medical Research Council MC_PC_U127561128Medical Research Council MC_U127527198Medical Research Council MC_U127584475Wellcome TrustWellcome Trust 061858Wellcome Trust 061860Wellcome Trust 068545/Z/02Wellcome Trust 091157Wellcome Trust 091388
6 · The paper itself

Abstract

Age-related macular degeneration (AMD) is a leading cause of visual loss in Western populations. Susceptibility is influenced by age, environmental and genetic factors. Known genetic risk loci do not account for all the heritability. We therefore carried out a genome-wide association study of AMD in the UK population with 893 cases of advanced AMD and 2199 controls. This showed an association with the well-established AMD risk loci ARMS2 (age-related maculopathy susceptibility 2)-HTRA1 (HtrA serine peptidase 1) (P =2.7 × 10(-72)), CFH (complement factor H) (P =2.3 × 10(-47)), C2 (complement component 2)-CFB (complement factor B) (P =5.2 × 10(-9)), C3 (complement component 3) (P =2.2 × 10(-3)) and CFI (P =3.6 × 10(-3)) and with more recently reported risk loci at VEGFA (P =1.2 × 10(-3)) and LIPC (hepatic lipase) (P =0.04). Using a replication sample of 1411 advanced AMD cases and 1431 examined controls, we confirmed a novel association between AMD and single-nucleotide polymorphisms on chromosome 6p21.3 at TNXB (tenascin XB)-FKBPL (FK506 binding protein like) [rs12153855/rs9391734; discovery P =4.3 × 10(-7), replication P =3.0 × 10(-4), combined P =1.3 × 10(-9), odds ratio (OR) = 1.4, 95% confidence interval (CI) = 1.3-1.6] and the neighbouring gene NOTCH4 (Notch 4) (rs2071277; discovery P =3.2 × 10(-8), replication P =3.8 × 10(-5), combined P =2.0 × 10(-11), OR = 1.3, 95% CI = 1.2-1.4). These associations remained significant in conditional analyses which included the adjacent C2-CFB locus. TNXB, FKBPL and NOTCH4 are all plausible AMD susceptibility genes, but further research will be needed to identify the causal variants and determine whether any of these genes are involved in the pathogenesis of AMD.

Indexed as

Chromosomes, Human, Pair 6Genome-Wide Association StudyAgedAged, 80 and overCase-Control StudiesFemaleGenetic LociGenetic Predisposition to DiseaseHaplotypesHumansImmunophilinsLinear ModelsLogistic ModelsMacular DegenerationMaleOdds RatioFKBPL protein, humanImmunophilinsNOTCH4 protein, humanProto-Oncogene ProteinsReceptor, Notch4Receptors, NotchTacrolimus Binding ProteinsTenascintenascin X

Identifiers

PMID22694956
PMCPMC3428154
OpenAlexW2111825522

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.