ArticlePLoS genetics2011
Integrating genome-wide genetic variations and monocyte expression data reveals trans-regulated gene modules in humans.
Article in PLoS genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 2 of them syntheses that pooled it.
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Who cites it
82 citing papers in PubMed, 2 syntheses or guidelines pooled it, 152 citations in OpenAlex.
- A genomic exploration identifies mechanisms that may explain adverse cardiovascular effects of COX-2 inhibitors.Scientific reports · 2017Pooled it
- Brain expression genome-wide association study (eGWAS) identifies human disease-associated variants.PLoS genetics · 2012Pooled it
- Pharmacogenomic characterization of gemcitabine response--a framework for data integration to enable personalized medicine.Pharmacogenetics and genomics · 2014Trial
- Genome-wide identification of expression quantitative trait loci (eQTLs) in human heart.PloS one · 2014Trial
- Multi-tissue multi-omics integration reveals tissue-specific pathways, gene networks and drug candidates for type 1 diabetes.Diabetologia · 2026Article
- Independent component analysis deciphers the genetic basis of cotton fiber elongation through eQTLs and sQTLs.Journal of advanced research · 2026Article
- GWAS-based population genetic analysis identifies bZIP29 as a heterotic gene in maize.Plant communications · 2025Article
- Trans-eQTL mapping in gene sets identifies network effects of genetic variants.Cell genomics · 2024Article
- Secreted Protein Profiling of Human Aortic Smooth Muscle Cells Identifies Vascular Disease Associations.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- The relationship between extreme inter-individual variation in macrophage gene expression and genetic susceptibility to inflammatory bowel disease.Human genetics · 2024Article
- Association of RPS26 gene polymorphism with different types of diabetes in Chinese individuals.Journal of diabetes investigation · 2024Article
- Secreted protein profiling of human aortic smooth muscle cells identifies vascular disease associations.medRxiv : the preprint server for health sciences · 2023Article
- A role for heritable transcriptomic variation in maize adaptation to temperate environments.Genome biology · 2023Article
- Natural Killer cells demonstrate distinct eQTL and transcriptome-wide disease associations, highlighting their role in autoimmunity.Nature communications · 2022Article
- Comparison of confound adjustment methods in the construction of gene co-expression networks.Genome biology · 2022Article
- Multi-omic insights into Parkinson's Disease: From genetic associations to functional mechanisms.Neurobiology of disease · 2022Review
- Article
- Tribbles 3 deficiency promotes atherosclerotic fibrous cap thickening and macrophage-mediated extracellular matrix remodelling.Frontiers in cardiovascular medicine · 2022Article
- TRIB1 regulates tumor growth via controlling tumor-associated macrophage phenotypes and is associated with breast cancer survival and treatment response.Theranostics · 2022Article
- EPISPOT: An epigenome-driven approach for detecting and interpreting hotspots in molecular QTL studies.American journal of human genetics · 2021Article
22 more citing papers are in PubMed but not listed here.
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Authors and funding
36 authors at 8 institutions in 4 countries.
Funding
Abstract
One major expectation from the transcriptome in humans is to characterize the biological basis of associations identified by genome-wide association studies. So far, few cis expression quantitative trait loci (eQTLs) have been reliably related to disease susceptibility. Trans-regulating mechanisms may play a more prominent role in disease susceptibility. We analyzed 12,808 genes detected in at least 5% of circulating monocyte samples from a population-based sample of 1,490 European unrelated subjects. We applied a method of extraction of expression patterns-independent component analysis-to identify sets of co-regulated genes. These patterns were then related to 675,350 SNPs to identify major trans-acting regulators. We detected three genomic regions significantly associated with co-regulated gene modules. Association of these loci with multiple expression traits was replicated in Cardiogenics, an independent study in which expression profiles of monocytes were available in 758 subjects. The locus 12q13 (lead SNP rs11171739), previously identified as a type 1 diabetes locus, was associated with a pattern including two cis eQTLs, RPS26 and SUOX, and 5 trans eQTLs, one of which (MADCAM1) is a potential candidate for mediating T1D susceptibility. The locus 12q24 (lead SNP rs653178), which has demonstrated extensive disease pleiotropy, including type 1 diabetes, hypertension, and celiac disease, was associated to a pattern strongly correlating to blood pressure level. The strongest trans eQTL in this pattern was CRIP1, a known marker of cellular proliferation in cancer. The locus 12q15 (lead SNP rs11177644) was associated with a pattern driven by two cis eQTLs, LYZ and YEATS4, and including 34 trans eQTLs, several of them tumor-related genes. This study shows that a method exploiting the structure of co-expressions among genes can help identify genomic regions involved in trans regulation of sets of genes and can provide clues for understanding the mechanisms linking genome-wide association loci to disease.
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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.