ArticleGenome medicine2020
Whole blood co-expression modules associate with metabolic traits and type 2 diabetes: an IMI-DIRECT study.
Article in Genome medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 12 citations in OpenAlex.
- High fat diet remodels the gene regulatory networks in the preoptic area.Scientific reports · 2026Article
- Network analysis of plasma proteomes in affective disorders.Translational psychiatry · 2023Article
- Patients with schizophrenia and bipolar disorder display a similar global gene expression signature in whole blood that reflects elevated proportion of immature neutrophil cells with association to lipid changes.Translational psychiatry · 2023Article
- Discovery of drug-omics associations in type 2 diabetes with generative deep-learning models.Nature biotechnology · 2023Article
- Indolepropionic Acid, a Gut Bacteria-Produced Tryptophan Metabolite and the Risk of Type 2 Diabetes and Non-Alcoholic Fatty Liver Disease.Nutrients · 2022Review
- Gene co-expression architecture in peripheral blood in a cohort of remitted first-episode schizophrenia patients.Schizophrenia (Heidelberg, Germany) · 2022Article
- Proteomics in thrombosis research.Research and practice in thrombosis and haemostasis · 2022Article
- Omics era in type 2 diabetes: From childhood to adulthood.World journal of diabetes · 2021Review
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Authors and funding
56 authors at 20 institutions in 10 countries.
Funding
Abstract
backgroundThe rising prevalence of type 2 diabetes (T2D) poses a major global challenge. It remains unresolved to what extent transcriptomic signatures of metabolic dysregulation and T2D can be observed in easily accessible tissues such as blood. Additionally, large-scale human studies are required to further our understanding of the putative inflammatory component of insulin resistance and T2D. Here we used transcriptomics data from individuals with (n = 789) and without (n = 2127) T2D from the IMI-DIRECT cohorts to describe the co-expression structure of whole blood that mainly reflects processes and cell types of the immune system, and how it relates to metabolically relevant clinical traits and T2D.
methodsClusters of co-expressed genes were identified in the non-diabetic IMI-DIRECT cohort and evaluated with regard to stability, as well as preservation and rewiring in the cohort of individuals with T2D. We performed functional and immune cell signature enrichment analyses, and a genome-wide association study to describe the genetic regulation of the modules. Phenotypic and trans-omics associations of the transcriptomic modules were investigated across both IMI-DIRECT cohorts.
resultsWe identified 55 whole blood co-expression modules, some of which clustered in larger super-modules. We identified a large number of associations between these transcriptomic modules and measures of insulin action and glucose tolerance. Some of the metabolically linked modules reflect neutrophil-lymphocyte ratio in blood while others are independent of white blood cell estimates, including a module of genes encoding neutrophil granule proteins with antibacterial properties for which the strongest associations with clinical traits and T2D status were observed. Through the integration of genetic and multi-omics data, we provide a holistic view of the regulation and molecular context of whole blood transcriptomic modules. We furthermore identified an overlap between genetic signals for T2D and co-expression modules involved in type II interferon signaling.
conclusionsOur results offer a large-scale map of whole blood transcriptomic modules in the context of metabolic disease and point to novel biological candidates for future studies related to T2D.
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