한빛사 논문
Kyung Won Kim MD, PhDa,∗, Sang-Cheol Park PhDb,∗, Hyung-Ju Cho MD, PhDc,∗, Haerin Jang BSa, Jaehyun Park BSd, Hyo Sup Shim MD, PhDe, Eun Gyul Kim MSa, Mi Na Kim PhDa, Jung Yeon Hong PhDa, Yoon Hee Kim MD, PhDf, Sanghun Lee PhDg, Scott T. Weiss MD PhDk, Chang-Hoon Kim MD, PhDc,#, Sungho Won PhDb,d,j,#, Myung Hyun Sohn MD, PhDa,∗,#
aDepartment of Pediatrics, Severance Hospital, Institute of Allergy, Institute for Immunology and Immunological Diseases, Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea
bInstitute of Health and Environment, Seoul National University, Seoul, Republic of Korea
cDepartment of Otorhinolaryngology, The Airway Mucus Institute, Korea Mouse Phenotyping Center (KMPC), Taste Research Center, Yonsei University College of Medicine, Seoul, Republic of Korea
dInterdisciplinary Program for Bioinformatics, College of Natural Science, Seoul National University, Seoul, South Korea
eDepartment of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
fDepartment of Pediatrics, Gangnam Severance Hospital, Institute of Allergy, Yonsei University College of Medicine, Seoul, Republic of Korea
gDepartment of Medical Consilience, Graduate School, Dankook Univeristy, Yongin, Republic of Korea
kChanning Division of Network Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
jDepartment of Public Health Sciences, Institute of Health and Environment, Interdisciplinary Program of Bioinformatics, College of Natural Sciences, Seoul National University, Seoul, Republic of Korea
∗These authors contributed equally to this work.
#Corresponding author
Abstract
Background
The relationship between allergic and eosinophilic inflammation, either systemic or local, remains unclear in allergic diseases.background
Objective
We performed combined genome-wide (GWAS) and epigenome-wide association studies (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 including 18 normal nasal tissues. 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 that genetically affect atopy. A direct association was observed between MSI2 SNPs and atopy, as well as the 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 including CAMK1D with enriched DMPs directly contributing to tissue eosinophilia at the gene level. The GO terms of the identified genes for both phenotypes encompassed immune-related terms.results
Conclusion
The 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, a harmonized effect of these genes is expected to influence immune responses.conclusion
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