ArticleProceedings of the National Academy of Sciences of the United States of America2012
Expression-based genome-wide association study links the receptor CD44 in adipose tissue with type 2 diabetes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers, 4 of them syntheses that pooled it.
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Who cites it
104 citing papers in PubMed, 4 syntheses or guidelines pooled it, 169 citations in OpenAlex.
- Pooled it
- Expression-Based Genome-Wide Association Study Links Vitamin D-Binding Protein With Autoantigenicity in Type 1 Diabetes.Diabetes · 2016Pooled it
- Role of innate immunity-triggered pathways in the pathogenesis of Sickle Cell Disease: a meta-analysis of gene expression studies.Scientific reports · 2015Pooled it
- Meta-analysis of molecular response of kidney to ischemia reperfusion injury for the identification of new candidate genes.BMC nephrology · 2013Pooled it
- An integrated transcriptomic and epigenomic analysis identifies CD44 gene as a potential biomarker for weight loss within an energy-restricted program.European journal of nutrition · 2019Trial
- Reanalysis of the Rituximab in ANCA-Associated Vasculitis trial identifies granulocyte subsets as a novel early marker of successful treatment.Arthritis research & therapy · 2015Trial
- From matrix to nucleus: CD44 as a central regulator of inflammaging, autophagy, and tissue homeostasis.Biogerontology · 2026Review
- Genetic underpinnings of type-2 diabetes (T2D) with colorectal cancer (CRC): In-silico discovery of common molecular signatures, pathogenetic processes and therapeutic candidates.Journal, genetic engineering & biotechnology · 2026Article
- Shared molecular mechanisms between type 2 diabetes and thyroid cancer: integrated bioinformatics insights for prognostic biomarker discovery.Endocrine connections · 2025Article
- Identification and Validation of Genes Involved in Energy Metabolism in Polycystic Ovary Syndrome.Iranian journal of biotechnology · 2025Article
- Differences in splicing factors may predict type 2 diabetes remission in the CORDIOPREV study.iScience · 2025Article
- Hidden pathway: the role of extracellular matrix in type 2 diabetes mellitus-related sarcopenia.Frontiers in endocrinology · 2025Review
- Disease-specific signatures of circulating extracellular vesicles detected by the surface plasmon resonance imaging: a pilot study.Extracellular vesicles and circulating nucleic acids · 2025Article
- Article
- Beneficial Effects of Echinacoside on Cognitive Impairment and Diabetes in Type 2 Diabetic db/db Mice.Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association · 2024Article
- Deletion of CD44 promotes adipogenesis by regulating PPARγ and cell cycle-related pathways.The Journal of endocrinology · 2024Article
- Unveiling the dynamics of acetylation and phosphorylation in SGBS and 3T3-L1 adipogenesis.iScience · 2024Article
- Inhibition of hyaluronan synthesis prevents β-cell loss in obesity-associated type 2 diabetes.Matrix biology : journal of the International Society for Matrix Biology · 2023Article
- Unraveling adipose tissue proteomic landscapes in severe obesity: insights into metabolic complications and potential biomarkers.American journal of physiology. Endocrinology and metabolism · 2023Article
- Identification of ferroptosis-related genes in type 2 diabetes mellitus based on machine learning.Immunity, inflammation and disease · 2023Article
44 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
Abstract
Type 2 diabetes (T2D) is a complex, polygenic disease affecting nearly 300 million people worldwide. T2D is primarily characterized by insulin resistance, and growing evidence has indicated the causative link between adipose tissue inflammation and the development of insulin resistance. Genetic association studies have successfully revealed a number of important genes consistently associated with T2D to date. However, these robust T2D-associated genes do not fully elucidate the mechanisms underlying the development and progression of the disease. Here, we report an alternative approach, gene expression-based genome-wide association study (eGWAS): searching for genes repeatedly implicated in functional microarray experiments (often publicly available). We performed an eGWAS across 130 independent experiments (totally 1,175 T2D case-control microarrays) to find additional genes implicated in the molecular pathogenesis of T2D and identified the immune-cell receptor CD44 as our top candidate (P = 8.5 × 10(-20)). We found CD44 deficiency in a diabetic mouse model ameliorates insulin resistance and adipose tissue inflammation and also found that anti-CD44 antibody treatment decreases blood glucose levels and adipose tissue macrophage accumulation in a high-fat, diet-fed mouse model. Further, in humans, we observed CD44 is expressed in inflammatory cells in obese adipose tissue and discovered serum CD44 levels were positively correlated with insulin resistance and glycemic control. CD44 likely plays a causative role in the development of adipose tissue inflammation and insulin resistance in rodents and humans. Genes repeatedly implicated in publicly available experimental data may have unique functionally important roles in T2D and other complex diseases.
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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.