ArticlePLoS genetics2016
Epistatic Gene-Based Interaction Analyses for Glaucoma in eMERGE and NEIGHBOR Consortium.
Article in PLoS genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03394859 (Electronic Medical Records and Genomics), which is not on this map. Cited by 24 papers.
What it found
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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.
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.
Electronic Medical Records and Genomics (eMERGE) Phase III
Who cites it
24 citing papers in PubMed, 43 citations in OpenAlex.
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- Functional genomic analysis delineates regulatory mechanisms of GWAS-identified bipolar disorder risk variants.Genome medicine · 2022Article
- Functional genomics elucidates regulatory mechanisms of Parkinson's disease-associated variants.BMC medicine · 2022Article
- Identification of Missense Extracellular Matrix Gene Variants in a Large Glaucoma Pedigree and Investigation of the N700S Thrombospondin-1 Variant in Normal and Glaucomatous Trabecular Meshwork Cells.Current eye research · 2022Article
- Identifying developmental stuttering and associated comorbidities in electronic health records and creating a phenome risk classifier.Journal of fluency disorders · 2021Article
- Normal and glaucomatous outflow regulation.Progress in retinal and eye research · 2021Review
- Updates on Genes and Genetic Mechanisms Implicated in Primary Angle-Closure Glaucoma.The application of clinical genetics · 2021Review
- A Novel Mapping Strategy Utilizing Mouse Chromosome Substitution Strains Identifies Multiple Epistatic Interactions That Regulate Complex Traits.G3 (Bethesda, Md.) · 2020Article
- SNCA and mTOR Pathway Single Nucleotide Polymorphisms Interact to Modulate the Age at Onset of Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2019Article
- The eMERGE genotype set of 83,717 subjects imputed to ~40 million variants genome wide and association with the herpes zoster medical record phenotype.Genetic epidemiology · 2019Article
- Genetic Architecture of Primary Open-Angle Glaucoma in Individuals of African Descent: The African Descent and Glaucoma Evaluation Study III.Ophthalmology · 2019Article
- Full genetic analysis for genome-wide association study of Fangji: a powerful approach for effectively dissecting the molecular architecture of personalized traditional Chinese medicine.Acta pharmacologica Sinica · 2018Review
- Leveraging epigenomics and contactomics data to investigate SNP pairs in GWAS.Human genetics · 2018Article
- The search for gene-gene interactions in genome-wide association studies: challenges in abundance of methods, practical considerations, and biological interpretation.Annals of translational medicine · 2018Article
- Genomic loci modulating retinal ganglion cell death following elevated IOP in the mouse.Experimental eye research · 2018Article
- Review
- HEDD: Human Enhancer Disease Database.Nucleic acids research · 2018Article
- Improving machine learning reproducibility in genetic association studies with proportional instance cross validation (PICV).BioData mining · 2018Article
- Leveraging putative enhancer-promoter interactions to investigate two-way epistasis in Type 2 Diabetes GWAS.Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing · 2018Article
- Widespread epistasis regulates glucose homeostasis and gene expression.PLoS genetics · 2017Article
Corrections and comments
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Authors and funding
17 authors at 9 institutions in 2 countries.
Funding
Abstract
Primary open angle glaucoma (POAG) is a complex disease and is one of the major leading causes of blindness worldwide. Genome-wide association studies have successfully identified several common variants associated with glaucoma; however, most of these variants only explain a small proportion of the genetic risk. Apart from the standard approach to identify main effects of variants across the genome, it is believed that gene-gene interactions can help elucidate part of the missing heritability by allowing for the test of interactions between genetic variants to mimic the complex nature of biology. To explain the etiology of glaucoma, we first performed a genome-wide association study (GWAS) on glaucoma case-control samples obtained from electronic medical records (EMR) to establish the utility of EMR data in detecting non-spurious and relevant associations; this analysis was aimed at confirming already known associations with glaucoma and validating the EMR derived glaucoma phenotype. Our findings from GWAS suggest consistent evidence of several known associations in POAG. We then performed an interaction analysis for variants found to be marginally associated with glaucoma (SNPs with main effect p-value <0.01) and observed interesting findings in the electronic MEdical Records and GEnomics Network (eMERGE) network dataset. Genes from the top epistatic interactions from eMERGE data (Likelihood Ratio Test i.e. LRT p-value <1e-05) were then tested for replication in the NEIGHBOR consortium dataset. To replicate our findings, we performed a gene-based SNP-SNP interaction analysis in NEIGHBOR and observed significant gene-gene interactions (p-value <0.001) among the top 17 gene-gene models identified in the discovery phase. Variants from gene-gene interaction analysis that we found to be associated with POAG explain 3.5% of additional genetic variance in eMERGE dataset above what is explained by the SNPs in genes that are replicated from previous GWAS studies (which was only 2.1% variance explained in eMERGE dataset); in the NEIGHBOR dataset, adding replicated SNPs from gene-gene interaction analysis explain 3.4% of total variance whereas GWAS SNPs alone explain only 2.8% of variance. Exploring gene-gene interactions may provide additional insights into many complex traits when explored in properly designed and powered association studies.
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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.