ArticlePLoS genetics2023
Transcriptome-wide gene-gene interaction associations elucidate pathways and functional enrichment of complex traits.
Article in PLoS genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.
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.
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Who cites it
6 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Loci on chromosome 20 interact with rs16969968 to influence cigarettes per day in European ancestry individuals.Drug and alcohol dependence · 2024Pooled it
- A simple approach for multiple observations improves power to detect genetic effects and genomic prediction accuracy.HGG advances · 2026Article
- Exploring Random Forest in Genetic Risk Score Construction.Genetic epidemiology · 2025Article
- A simple approach for multiple observations improves power to detect genetic effects and genomic prediction accuracy.medRxiv : the preprint server for health sciences · 2025Article
- PPIxGPN: plasma proteomic profiling of neurodegenerative biomarkers with protein-protein interaction-based eXplainable graph propagational network.Briefings in bioinformatics · 2025Article
- Combinatorial transcriptomic and genetic dissection of insulin/IGF-1 signaling-regulated longevity in Caenorhabditis elegans.Aging cell · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
Abstract
It remains unknown to what extent gene-gene interactions contribute to complex traits. Here, we introduce a new approach using predicted gene expression to perform exhaustive transcriptome-wide interaction studies (TWISs) for multiple traits across all pairs of genes expressed in several tissue types. Using imputed transcriptomes, we simultaneously reduce the computational challenge and improve interpretability and statistical power. We discover (in the UK Biobank) and replicate (in independent cohorts) several interaction associations, and find several hub genes with numerous interactions. We also demonstrate that TWIS can identify novel associated genes because genes with many or strong interactions have smaller single-locus model effect sizes. Finally, we develop a method to test gene set enrichment of TWIS associations (E-TWIS), finding numerous pathways and networks enriched in interaction associations. Epistasis is may be widespread, and our procedure represents a tractable framework for beginning to explore gene interactions and identify novel genomic targets.
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What Socratic holds
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 Socratic graph.