| 게재년월 | 2021/04 |
|---|---|
| 논문제목 | Integrated genetic and epigenetic analyses uncover MSI2 association with allergic inflammation. |
| 참여교수 | 손명현 |
| 학술지명 | JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY |
| 초록 | Background: The relationship between allergic and eosinophilic inflammation, either systemic or local, in allergic diseases remains unclear. Objective: 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. Methods: 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. Results: EWAS identified genes, including Musashi RNA binding protein 2 (MSI2), associated with atopy, which contained enriched DMPs that genetically affect atopy. A direct association was observed between MSI2 single-nucleotide polymorphisms and atopy, as was a causal effect of changes in MSI2 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 CAMK1D. The gene ontology terms of the identified genes for both phenotypes encompassed immune-related terms. Conclusion: EWAS combined with GWAS identified novel candidate genes, especially the methylation of MSI2, 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. |
| 게재정보 | J Allergy Clin Immunol. 2021 Apr;147(4):1453-1463 |
| 총저자명 | Kyung Won Kim, Sang Cheol Park, Hyung Ju Cho, Hae rin Jang, Jae hyun Park, Hyo Sup Shim, Eun Gyul Kim, Mi Na Kim, Jung Yeon Hong, Yoon Hee Kim, Sang hun Lee, Chang Hoon Kim, Sung ho Won, Myung Hyun Sohn |
