Gene-based analysis of regulatory variants identifies four putative novel asthma risk genes related to nucleotide synthesis and signaling

Using a new method for gene-based analysis of GWAS results, we identified a genetic association between asthma risk and eQTLs for B4GALT3 and USMG5, which are involved in the production of UDP-galactose and ATP respectively, and P2RY13 and P2RY14, two G protein-coupled receptors activated respectively by ADP and UDP-sugars. Functional studies in the mouse show that activation of P2ry13 or P2ry14 induces the release of IL-33 and eosinophil infiltration into the lungs, in the absence of allergen stimulation. Functional studies that characterize in depth the contribution of these four genes to asthma pathophysiology are warranted.

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