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• W3048658963 abstract "<h3>Background</h3> The relationship between allergic and eosinophilic inflammation, either systemic or local, in allergic diseases remains unclear. <h3>Objective</h3> We performed combined genome-wide association study (GWAS) and epigenome-wide (EWAS) for atopy and tissue eosinophilia to identify both genetic and epigenetic signatures between systemic and local allergic inflammation, and to capture global patterns of gene regulation. <h3>Methods</h3> We included 126 subjects for atopy analysis and 147 for tissue eosinophilia analysis, as well as 18 normal nasal tissue samples. We identified differentially methylated positions (DMPs) and genes associated with atopy and tissue eosinophilia. Furthermore, we performed mendelian randomization analysis and penalized regression along with replication in an independent cohort. <h3>Results</h3> EWAS identified genes, including Musashi RNA binding protein 2 <i>(MSI2)</i>, associated with atopy, which contained enriched DMPs that genetically affect atopy. A direct association was observed between <i>MSI2</i> single-nucleotide polymorphisms and atopy, as was a causal effect of changes in <i>MSI2</i> expression and methylation on atopy, which was replicated in a Costa Rican population. Regarding tissue eosinophilia, EWAS identified genes with enriched DMPs directly contributing to tissue eosinophilia at the gene level, including <i>CAMK1D</i>. The gene ontology terms of the identified genes for both phenotypes encompassed immune-related terms. <h3>Conclusion</h3> EWAS combined with GWAS identified novel candidate genes, especially the methylation of <i>MSI2</i>, contributing to systemic allergic inflammation. Certain genes displayed a greater association with either systemic or local allergic inflammation; however, it is expected that a harmonized effect of these genes influences immune responses." @default.
• W3048658963 created "2020-08-18" @default.
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• W3048658963 date "2021-04-01" @default.
• W3048658963 modified "2023-10-16" @default.
• W3048658963 title "Integrated genetic and epigenetic analyses uncover MSI2 association with allergic inflammation" @default.
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• W3048658963 doi "https://doi.org/10.1016/j.jaci.2020.06.040" @default.
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