ArticleThe Journal of allergy and clinical immunology2017
Gene-based analysis of regulatory variants identifies 4 putative novel asthma risk genes related to nucleotide synthesis and signaling.
Article in The Journal of allergy and clinical immunology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 3 of them syntheses that pooled it.
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Who cites it
40 citing papers in PubMed, 3 syntheses or guidelines pooled it, 72 citations in OpenAlex.
- ZRANB3 is an African-specific type 2 diabetes locus associated with beta-cell mass and insulin response.Nature communications · 2019Pooled it
- Association study in African-admixed populations across the Americas recapitulates asthma risk loci in non-African populations.Nature communications · 2019Pooled it
- Genome-wide association meta-analysis highlights light-induced signaling as a driver for refractive error.Nature genetics · 2018Pooled it
- Modulation of blood inflammatory markers by benralizumab in patients with eosinophilic airway diseases.Respiratory research · 2019Trial
- Stimulation of platelet P2YBritish journal of pharmacology · 2024Article
- Evaluating 17 methods incorporating biological function with GWAS summary statistics to accelerate discovery demonstrates a tradeoff between high sensitivity and high positive predictive value.Communications biology · 2023Article
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- Sex differences in the genetics of sarcoidosis across European and African ancestry populations.Frontiers in medicine · 2023Article
- Reduced urine volume and changed renal sphingolipid metabolism in P2ry14-deficient mice.Frontiers in cell and developmental biology · 2023Article
- Inhibiting the P2YPurinergic signalling · 2022Article
- eQTL Set-Based Association Analysis Identifies Novel Susceptibility Loci for Barrett Esophagus and Esophageal Adenocarcinoma.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2022Article
- Multiomics analysis identifies BIRC3 as a novel glucocorticoid response-associated gene.The Journal of allergy and clinical immunology · 2022Article
- Targeting the P2YAmerican journal of respiratory and critical care medicine · 2022Article
- An Alarmin Role for P2YAmerican journal of respiratory and critical care medicine · 2022Article
- GPR105-Targeted Therapy Promotes Gout Resolution as a Switch Between NETosis and Apoptosis of Neutrophils.Frontiers in immunology · 2022Article
- Leveraging auxiliary data from arbitrary distributions to boost GWAS discovery with Flexible cFDR.PLoS genetics · 2021Article
- UDP-glucose and P2Y14 receptor amplify allergen-induced airway eosinophilia.The Journal of clinical investigation · 2021Article
- Uridine diphosphate-glucose/P2Y14R axis is a nonchemokine pathway that selectively promotes eosinophil accumulation.The Journal of clinical investigation · 2021Article
- The influence of human genetic variation on Epstein-Barr virus sequence diversity.Scientific reports · 2021Article
Corrections and comments
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Authors and funding
23 authors at 12 institutions in 3 countries.
Funding
Abstract
backgroundHundreds of genetic variants are thought to contribute to variation in asthma risk by modulating gene expression. Methods that increase the power of genome-wide association studies (GWASs) to identify risk-associated variants are needed.
objectiveWe sought to develop a method that aggregates the evidence for association with disease risk across expression quantitative trait loci (eQTLs) of a gene and use this approach to identify asthma risk genes.
methodsWe developed a gene-based test and software package called EUGENE that (1) is applicable to GWAS summary statistics; (2) considers both cis- and trans-eQTLs; (3) incorporates eQTLs identified in different tissues; and (4) uses simulations to account for multiple testing. We applied this approach to 2 published asthma GWASs (combined n = 46,044) and used mouse studies to provide initial functional insights into 2 genes with novel genetic associations.
resultsWe tested the association between asthma and 17,190 genes that were found to have cis- and/or trans-eQTLs across 16 published eQTL studies. At an empirical FDR of 5%, 48 genes were associated with asthma risk. Of these, for 37, the association was driven by eQTLs located in established risk loci for allergic disease, including 6 genes not previously implicated in disease cause (eg, LIMS1, TINF2, and SAFB). The remaining 11 significant genes represent potential novel genetic associations with asthma. The association with 4 of these replicated in an independent GWAS: B4GALT3, USMG5, P2RY13, and P2RY14, which are genes involved in nucleotide synthesis or nucleotide-dependent cell activation. In mouse studies, P2ry13 and P2ry14-purinergic receptors activated by adenosine 5-diphosphate and UDP-sugars, respectively-were upregulated after allergen challenge, notably in airway epithelial cells, eosinophils, and neutrophils. Intranasal exposure with receptor agonists induced the release of IL-33 and subsequent eosinophil infiltration into the lungs.
conclusionWe identified novel associations between asthma and eQTLs for 4 genes related to nucleotide synthesis/signaling and demonstrated the power of gene-based analyses of GWASs.
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Registered trials
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