ArticleAmerican journal of human genetics2019
GRIK5 Genetically Regulated Expression Associated with Eye and Vascular Phenomes: Discovery through Iteration among Biobanks, Electronic Health Records, and Zebrafish.
Article in American journal of human genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 2 of them syntheses that pooled it.
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Who cites it
25 citing papers in PubMed, 2 syntheses or guidelines pooled it, 34 citations in OpenAlex.
- Novel ancestry-specific primary open-angle glaucoma loci and shared biology with vascular mechanisms and cell proliferation.Cell reports. Medicine · 2024Pooled it
- Integration of genomics and transcriptomics predicts diabetic retinopathy susceptibility genes.eLife · 2020Pooled it
- Succinate supplementation ameliorates musculoskeletal defects caused by PLOD3 mutations in a BCARD syndrome model.Genome medicine · 2026Article
- Expanding the Genetic Landscape of Craniofacial Anomalies Through Transcriptome-Wide Association Studies.Research square · 2025Article
- Building a framework for reproducibility: the case for standardized data reporting and metadata integration in zebrafish research.Disease models & mechanisms · 2025Article
- Expanding the Genetic Landscape of Craniofacial Anomalies Through Transcriptome-Wide Association Studies.Research square · 2025Article
- A blood- and brain-based EWAS of smoking.Nature communications · 2025Article
- Multiomics reveal key inflammatory drivers of severe obesity: IL4R, LILRA5, and OSM.Cell genomics · 2025Article
- Gene and phenome-based analysis of the shared genetic architecture of eye diseases.American journal of human genetics · 2025Article
- Identification of novel genetic loci related to dromedary camel (Camelus dromedarius) morphometrics, biomechanics, and behavior by genome-wide association studies.BMC veterinary research · 2024Article
- Integration of estimated regional gene expression with neuroimaging and clinical phenotypes at biobank scale.PLoS biology · 2024Article
- Transcriptome-Wide Association Studies (TWAS): Methodologies, Applications, and Challenges.Current protocols · 2024Article
- Changes in ADAR RNA editing patterns in CMV and ZIKV congenital infections.BMC genomics · 2023Article
- Rgp1 contributes to craniofacial cartilage development and Rab8a-mediated collagen II secretion.Frontiers in endocrinology · 2023Article
- Biomarker Discovery for Meta-Classification of Melanoma Metastatic Progression Using Transfer Learning.Genes · 2022Article
- Best practices for multi-ancestry, meta-analytic transcriptome-wide association studies: Lessons from the Global Biobank Meta-analysis Initiative.Cell genomics · 2022Article
- The Genetic Architecture of Meat Quality Traits in a Crossbred Commercial Pig Population.Foods (Basel, Switzerland) · 2022Article
- Integrative transcriptomic, evolutionary, and causal inference framework for region-level analysis: Application to COVID-19.NPJ genomic medicine · 2022Article
- Phenome-Wide Association Studies.JAMA · 2022Article
- Using Phecodes for Research with the Electronic Health Record: From PheWAS to PheRS.Annual review of biomedical data science · 2021Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
Although the use of model systems for studying the mechanism of mutations that have a large effect is common, we highlight here the ways that zebrafish-model-system studies of a gene, GRIK5, that contributes to the polygenic liability to develop eye diseases have helped to illuminate a mechanism that implicates vascular biology in eye disease. A gene-expression prediction derived from a reference transcriptome panel applied to BioVU, a large electronic health record (EHR)-linked biobank at Vanderbilt University Medical Center, implicated reduced GRIK5 expression in diverse eye diseases. We tested the function of GRIK5 by depletion of its ortholog in zebrafish, and we observed reduced blood vessel numbers and integrity in the eye and increased vascular permeability. Analyses of EHRs in >2.6 million Vanderbilt subjects revealed significant comorbidity of eye and vascular diseases (relative risks 2-15); this comorbidity was confirmed in 150 million individuals from a large insurance claims dataset. Subsequent studies in >60,000 genotyped BioVU participants confirmed the association of reduced genetically predicted expression of GRIK5 with comorbid vascular and eye diseases. Our studies pioneer an approach that allows a rapid iteration of the discovery of gene-phenotype relationships to the primary genetic mechanism contributing to the pathophysiology of human disease. Our findings also add dimension to the understanding of the biology driven by glutamate receptors such as GRIK5 (also referred to as GLUK5 in protein form) and to mechanisms contributing to human eye diseases.
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Registered trials
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.