Trial reportPLoS genetics2014
Mediation analysis demonstrates that trans-eQTLs are often explained by cis-mediation: a genome-wide analysis among 1,800 South Asians.
Trial report in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
What it found
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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.
Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 113 citations in OpenAlex.
- Plasma cortisol-linked gene networks in hepatic and adipose tissues implicate corticosteroid-binding globulin in modulating tissue glucocorticoid action and cardiovascular risk.Frontiers in endocrinology · 2023Pooled it
- Co-occurring expression and methylation QTLs allow detection of common causal variants and shared biological mechanisms.Nature communications · 2018Trial
- Single-nucleus atlas of cell-type specific genetic regulation in the human brain.Nature genetics · 2026Article
- Co-expression-based models improve eQTL predictions for transcriptome-wide association studies and highlight new schizophrenia-associated genes.Nature genetics · 2026Article
- Transcription factors and candidate functional SNPs associated with variation in fatty acid composition from skeletal muscle of pigs.Animal genetics · 2025Article
- Causal network inference of cis- and trans-gene regulation of expression quantitative trait loci across human tissues.Genetics · 2025Article
- ADELLE: A global testing method for trans-eQTL mapping.PLoS genetics · 2025Article
- A brief guide to analyzing expression quantitative trait loci.Molecules and cells · 2024Review
- Quantitative omnigenic model discovers interpretable genome-wide associations.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Integrative cross-omics and cross-context analysis elucidates molecular links underlying genetic effects on complex traits.Nature communications · 2024Article
- Gene expression variation underlying tissue-specific responses to copper stress in Drosophila melanogaster.G3 (Bethesda, Md.) · 2024Article
- Systematic differences in discovery of genetic effects on gene expression and complex traits.Nature genetics · 2023Article
- Methods and Insights from Single-Cell Expression Quantitative Trait Loci.Annual review of genomics and human genetics · 2023Review
- The trouble with triples: Examining the impact of measurement error in mediation analysis.Genetics · 2023Article
- Methods for large-scale single mediator hypothesis testing: Possible choices and comparisons.Genetic epidemiology · 2023Review
- Illuminating links between cis-regulators and trans-acting variants in the human prefrontal cortex.Genome medicine · 2022Article
- Interpretation of the role of germline and somatic non-coding mutations in cancer: expression and chromatin conformation informed analysis.Clinical epigenetics · 2022Review
- Extreme phenotypic diversity in operant response to intravenous cocaine or saline infusion in the hybrid mouse diversity panel.Addiction biology · 2022Article
- Article
- Partitioning gene-mediated disease heritability without eQTLs.American journal of human genetics · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 6 institutions in 4 countries.
Funding
Abstract
A large fraction of human genes are regulated by genetic variation near the transcribed sequence (cis-eQTL, expression quantitative trait locus), and many cis-eQTLs have implications for human disease. Less is known regarding the effects of genetic variation on expression of distant genes (trans-eQTLs) and their biological mechanisms. In this work, we use genome-wide data on SNPs and array-based expression measures from mononuclear cells obtained from a population-based cohort of 1,799 Bangladeshi individuals to characterize cis- and trans-eQTLs and determine if observed trans-eQTL associations are mediated by expression of transcripts in cis with the SNPs showing trans-association, using Sobel tests of mediation. We observed 434 independent trans-eQTL associations at a false-discovery rate of 0.05, and 189 of these trans-eQTLs were also cis-eQTLs (enrichment P<0.0001). Among these 189 trans-eQTL associations, 39 were significantly attenuated after adjusting for a cis-mediator based on Sobel P<10-5. We attempted to replicate 21 of these mediation signals in two European cohorts, and while only 7 trans-eQTL associations were present in one or both cohorts, 6 showed evidence of cis-mediation. Analyses of simulated data show that complete mediation will be observed as partial mediation in the presence of mediator measurement error or imperfect LD between measured and causal variants. Our data demonstrates that trans-associations can become significantly stronger or switch directions after adjusting for a potential mediator. Using simulated data, we demonstrate that this phenomenon is expected in the presence of strong cis-trans confounding and when the measured cis-transcript is correlated with the true (unmeasured) mediator. In conclusion, by applying mediation analysis to eQTL data, we show that a substantial fraction of observed trans-eQTL associations can be explained by cis-mediation. Future studies should focus on understanding the mechanisms underlying widespread cis-mediation and their relevance to disease biology, as well as using mediation analysis to improve eQTL discovery.
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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.