Evidence map›Paper›PMID 25950802›Full record

ArticlePloS one2015

Netrin-1 - DCC Signaling Systems and Age-Related Macular Degeneration.

John Paul SanGiovanni, Jing Chen, Ankur S Gupta, Lois E H Smith, Przemyslaw Sapieha, Phil H Lee

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

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.1field-weighted citation impact, top 53% 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

2 citing papers in PubMed, 2 citations in OpenAlex.

  1. Article
  2. Risk factors and biomarkers of age-related macular degeneration.Progress in retinal and eye research · 2016
    Review
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

6 authors at 6 institutions in 2 countries.

John Paul SanGiovanniNational Institute of Alcohol Abuse and Alcoholism, Section on Nutritional Neuroscience, National Institutes of Health, Bethesda, MD, United States of America.
Jing ChenDepartment of Ophthalmology, Harvard Medical School, Boston Children's Hospital, Boston, MA, United States of America.
Ankur S GuptaUniversity of Texas Southwestern Medical Center at Dallas, Dallas, Texas, United States of America.
Lois E H SmithDepartment of Ophthalmology, Harvard Medical School, Boston Children's Hospital, Boston, MA, United States of America.
Przemyslaw SapiehaDepartment of Ophthalmology, Maisonneuve-Rosemont Hospital Research Centre, University of Montreal, Montreal, QC, Canada.
Phil H LeeAnalytic & Translational Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States of America.
Boston Children's Hospital · USHarvard University · USHôpital Maisonneuve-Rosemont · CAMassachusetts General Hospital · USNational Institute on Alcohol Abuse and Alcoholism · USThe University of Texas Southwestern Medical Center · US

Funding

SYNAPTIC MECHANISMS IN HIPPOCAMPAL EPILEPTOGENESISP30HD018655 · NICHD · CHILDREN'S HOSPITAL BOSTON · PI FAGIOLINI, MICHELA · 1985 to 2015
$26.2M
Dietary control of angiogenesis in retinopathy modelsR01EY017017 · NEI · BOSTON CHILDREN'S HOSPITAL · PI Zhongjie Fu, Lois Smith · 2006 to 2026
$11.8M
RORalpha mediates chronic subretinal inflammation associated with AMDR01EY024963 · NEI · BOSTON CHILDREN'S HOSPITAL · PI CHEN, JING · 2015 to 2025
$4.2M
Neuroimaging genetics to study social cognitive deficits in ASD and schizophreniaK99MH101367 · NIMH · MASSACHUSETTS GENERAL HOSPITAL · PI LEE, PHIL H. · 2014 to 2015
$237k
The roles of Frizzled-4 and Sox17 in retinal vascular development and maintenanceF32EY022274 · NEI · JOHNS HOPKINS UNIVERSITY · PI TISCHFIELD, MAX · 2012 to 2014
$163k
Canadian Institutes of Health Research 221478Intramural NIH HHSNEI NIH HHS F32 EY022274NEI NIH HHS R01 EY017017NEI NIH HHS R01 EY024963NICHD NIH HHS P30 HD018655NIMH NIH HHS K99 MH101367
6 · The paper itself

Abstract

We conducted a nested candidate gene study and pathway-based enrichment analysis on data from a multi-national 77,000-person project on the molecular genetics of age-related macular degeneration (AMD) to identify AMD-associated DNA-sequence variants in genes encoding constituents of a netrin-1 (NTN1)-based signaling pathway that converges on DNA-binding transcription complexes through a 3'-5'-cyclic adenosine monophosphate-calcineurin (cAMP-CN)-dependent axis. AMD-associated single nucleotide polymorphisms (SNPs) existed in 9 linkage disequilibrium-independent genomic regions; these included loci overlapping NTN1 (rs9899630, P ≤ 9.48 x 10(-5)), DCC (Deleted in Colorectal Cancer)--the gene encoding a primary NTN1 receptor (rs8097127, P ≤ 3.03 x 10(-5)), and 6 other netrin-related genes. Analysis of the NTN1-DCC pathway with exact methods demonstrated robust enrichment with AMD-associated SNPs (corrected P-value = 0.038), supporting the idea that processes driven by NTN1-DCC signaling systems operate in advanced AMD. The NTN1-DCC pathway contains targets of FDA-approved drugs and may offer promise for guiding applied clinical research on preventive and therapeutic interventions for AMD.

Indexed as

Signal TransductionDCC ReceptorHumansMacular DegenerationNerve Growth FactorsNetrin-1Receptors, Cell SurfaceTumor Suppressor ProteinsDCC protein, humanDCC ReceptorNerve Growth FactorsNetrin-1NTN1 protein, humanReceptors, Cell SurfaceTumor Suppressor Proteins

Identifiers

PMID25950802
PMCPMC4423995
OpenAlexW1917983040

What OpenQuestion holds

Textmetadata
LicenceCC0
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.