Evidence map›Paper›PMID 40801674›Full record

ArticleInvestigative ophthalmology & visual science2025

Whole Exome Sequencing Study Uncovers Novel Candidate Genes and Protein-Coding Variants for Cataract.

Dima L Chaar, Chen Jiang, Sarah Y Coomson, Matthieu Duot, Poorab Sangani, Thomas J Hoffmann, Eric Jorgenson, Robert B Hufnagel, Pirro Hysi, Salil A Lachke and 1 more

Abstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. 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

11 authors.

Dima L ChaarKaiser Permanente Northern California (KPNC), Division of Research, Pleasanton, California, United States.
Chen JiangKaiser Permanente Northern California (KPNC), Division of Research, Pleasanton, California, United States.
Sarah Y CoomsonDepartment of Biological Sciences, University of Delaware, Newark, Delaware, United States.
Matthieu DuotUniv Rennes, CNRS, IGDR (Institut de Génétique et Développement de Rennes), Rennes, France.
Poorab SanganiKPNC, Department of Ophthalmology, South San Francisco, California, United States.
Thomas J HoffmannInstitute for Human Genetics, University of California, San Francisco (UCSF), San Francisco, California, United States.
Eric JorgensonRegeneron Genetics Center, Tarrytown, New York, United States.
Robert B HufnagelDepartment of Genetics and Center for Integrated Healthcare Research, Kaiser Permanente Hawaii Region, Honolulu, Hawaii, United States.
Pirro HysiKing's College London, Section of Ophthalmology, School of Life Course Sciences, London, United Kingdom.
Salil A LachkeDepartment of Biological Sciences, University of Delaware, Newark, Delaware, United States.
Hélène ChoquetKaiser Permanente Northern California (KPNC), Division of Research, Pleasanton, California, United States.

Funding

A Resource for Genetic Epidemiology Research in Adult Health and AgingRC2AG036607 · NIA · KAISER FOUNDATION RESEARCH INSTITUTE · PI RISCH, NEIL J., SCHAEFER, CATHERINE ANN · 2009 to 2010
$24.8M
The Role of Genetic and Non-Genetic Factors and Causal Mechanisms Underlying Cataract Susceptibility For Risk PredictionR01EY033010 · NEI · KAISER FOUNDATION RESEARCH INSTITUTE · PI CHOQUET, HELENE, LACHKE, SALIL · 2022 to 2025
$1.6M
NEI NIH HHS R01 EY033010NIA NIH HHS RC2 AG036607
6 · The paper itself

Abstract

Purpose: To identify novel candidates for cataract and evaluate the contribution of protein-coding variants to cataract susceptibility. Methods: We first leveraged a publicly-available browser, Genebass, to extract significant gene-based and single-variant association results for cataract in UK Biobank exomes (30,550 cataract cases and 364,291 controls). We then validated findings using genome-wide association study (GWAS) summary statistics from the Genetic Epidemiology Research in Adult Health and Aging (GERA) cohort (28,092 cataract cases and 50,487 controls). Finally, we examined the expression of the prioritized genes in lens tissue using the iSyTE database. Results: Gene-based association testing identified four genes (KDM5B, COL2A1, MIP and CRYBB2) that were associated with cataract (P < 2.50 × 10-6), of which one (KDM5B) was neither previously reported to be associated with congenital cataract nor reported in GWAS. Single-variant association testing identified seven variants within six genes (BFSP2, ZNF800, MIP, HERC2, TSPAN10 and CPAMD8) that were associated with cataract (P < 1.00 × 10-8). Among the identified cataract variants, we found four missense, one synonymous, one frameshift, and one stop-gained variant. Associations at COL2A1, HERC2, and ZNF800 were validated in GERA. Importantly, majority of prioritized cataract genes were robustly expressed in iSyTE lens data and were enriched in structural constituent of eye lens, lens development in camera-type eye, visual perception, and collagen type II trimer pathways. Conclusions: Our results demonstrate the value of gene-based and single-variant association testing for understanding cataract etiology and uncovering novel genetic risk factors. Our findings also show that cataract-associated genes are significantly expressed in lens tissues and lens-related biological pathways.

Indexed as

CataractExome SequencingEye ProteinsGenetic Predisposition to DiseasePolymorphism, Single NucleotideAgedbeta-Crystallin B ChainFemaleGenome-Wide Association StudyHumansLens, CrystallineMaleMiddle Agedbeta-Crystallin B ChainEye Proteins

Identifiers

PMID40801674
PMCPMC12366868

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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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 Socratic graph.