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Integrated genetic and epigenetic analyses uncover MSI2 association with allergic inflammation

Authors
 Kyung Won Kim  ;  Sang-Cheol Park  ;  Hyung-Ju Cho  ;  Haerin Jang  ;  Jaehyun Park  ;  Hyo Sup Shim  ;  Eun Gyul Kim  ;  Mi Na Kim  ;  Jung Yeon Hong  ;  Yoon Hee Kim  ;  Sanghun Lee  ;  Scott T Weiss  ;  Chang-Hoon Kim  ;  Sungho Won  ;  Myung Hyun Sohn 
Citation
 JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY : Epub., 2020-08 
Journal Title
 JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 
ISSN
 0091-6749 
Issue Date
2020-08
Keywords
Atopy ; GWAS ; eosinophilia ; epigenetic ; genetic ; methylation
Abstract
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.
Full Text
https://www.sciencedirect.com/science/article/pii/S0091674920311064
DOI
10.1016/j.jaci.2020.06.040
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pediatrics (소아과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Won(김경원) ORCID logo https://orcid.org/0000-0003-4529-6135
Kim, Yoon Hee(김윤희) ORCID logo https://orcid.org/0000-0002-2149-8501
Kim, Chang Hoon(김창훈) ORCID logo https://orcid.org/0000-0003-1238-6396
Sohn, Myung Hyun(손명현) ORCID logo https://orcid.org/0000-0002-2478-487X
Shim, Hyo Sup(심효섭) ORCID logo https://orcid.org/0000-0002-5718-3624
Cho, Hyung Ju(조형주) ORCID logo https://orcid.org/0000-0002-2851-3225
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/180802
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