Evidence map›Paper›PMID 37079518›Full record

ArticlePloS one2023

Rare CIDEC coding variants enriched in age-related macular degeneration patients with small low-luminance deficit cause lipid droplet and fat storage defects.

Sehyun Kim, Amy Stockwell, Han Qin, Simon S Gao, Meredith Sagolla, Ivaylo Stoilov, Arthur Wuster, Phillip Lai, Brian L Yaspan, Marion Jeanne

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
1.4field-weighted citation impact, top 20% 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

3 citing papers in PubMed, 5 citations in OpenAlex.

  1. Review
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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

10 authors.

Sehyun KimDepartment of Neuroscience, Genentech Inc., South San Francisco, California, United States of America.
Amy StockwellDepartment of Human Genetics, Genentech Inc., South San Francisco, California, United States of America.
Han QinDepartment of Neuroscience, Genentech Inc., South San Francisco, California, United States of America.
Simon S GaoDepartment of Clinical Imaging, Genentech Inc., South San Francisco, California, United States of America.ORCID 0000-0002-7020-037X
Meredith SagollaDepartment of Research Pathology, Genentech Inc., South San Francisco, California, United States of America.
Ivaylo StoilovMedical Affairs Ophthalmology, Genentech Inc., South San Francisco, California, United States of America.
Arthur WusterDepartment of Human Genetics, Genentech Inc., South San Francisco, California, United States of America.
Phillip LaiEarly Clinical Development, Genentech Inc., South San Francisco, California, United States of America.
Brian L YaspanDepartment of Human Genetics, Genentech Inc., South San Francisco, California, United States of America.
Marion JeanneDepartment of Neuroscience, Genentech Inc., South San Francisco, California, United States of America.ORCID 0000-0001-7334-3061

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe basis of Age-related macular degeneration (AMD) genetic risk has been well documented; however, few studies have looked at genetic biomarkers of disease progression or treatment response within advanced AMD patients. Here we report the first genome-wide analysis of genetic determinants of low-luminance vision deficit (LLD), which is seen as predictive of visual acuity loss and anti-VEGF treatment response in neovascular AMD patients.

methodsAMD patients were separated into small- and large-LLD groups for comparison and whole genome sequencing was performed. Genetic determinants of LLD were assessed by common and rare variant genetic analysis. Follow-up functional analysis of rare coding variants identified by the burden test was then performed in vitro.

resultsWe identified four coding variants in the CIDEC gene. These rare variants were only present in patients with a small LLD, which has been previously shown to indicate better prognosis and better anti-VEGF treatment response. Our in vitro functional characterization of these CIDEC alleles revealed that all decrease the binding affinity between CIDEC and the lipid droplet fusion effectors PLIN1, RAB8A and AS160. The rare CIDEC alleles all cause a hypomorphic defect in lipid droplet fusion and enlargement, resulting in a decreased fat storage capability in adipocytes.

conclusionsAs we did not detect CIDEC expression in the ocular tissue affected by AMD, our results suggest that the CIDEC variants do not play a direct role in the eye and influence low-luminance vision deficit via an indirect and systemic effect related to fat storage capacity.

Indexed as

Vision, LowWet Macular DegenerationAngiogenesis InhibitorsApoptosis Regulatory ProteinsHumansLipid DropletsVascular Endothelial Growth Factor AVisual AcuityAngiogenesis InhibitorsApoptosis Regulatory ProteinsCIDEC protein, humanVascular Endothelial Growth Factor A

Identifiers

PMID37079518
PMCPMC10118094
OpenAlexW4366463060

What Socratic 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 Socratic graph.