The genome-wide association study of serum IgE levels demonstrated a shared genetic background in allergic diseases

Hsing-Fang Lu; Chen-Hsing Chou; Ying-Ju Lin; Shunsuke Uchiyama; Chikashi Terao; Yu-Wen Wang; Jai-Sing Yang; Ting-Yuan Liu; Henry Sung-Ching Wong; Sean Chun-Chang Chen; Fuu-Jen Tsai

doi:10.1016/j.clim.2024.109897

The genome-wide association study of serum IgE levels demonstrated a shared genetic background in allergic diseases

Clin Immunol. 2024 Mar:260:109897. doi: 10.1016/j.clim.2024.109897. Epub 2024 Jan 8.

Authors

Affiliations

¹ Department of Medical Research, China Medical University Hospital, Taichung 404327, Taiwan; Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
² PhD Program for Health Science and Industry, College of Health Care, China Medical University, Taichung, Taiwan; Department of Health Services Administration, China Medical University, Taichung, Taiwan.
³ Genetic Center, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan; School of Chinese Medicine, China Medical University, Taichung, Taiwan.
⁴ Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
⁵ Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan; Clinical Research Center, Shizuoka General Hospital, Shizuoka, Japan; The Department of Applied Genetics, The School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
⁶ Department of Medical Research, China Medical University Hospital, Taichung 404327, Taiwan.
⁷ Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, 404327, Taiwan.
⁸ Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
⁹ Department of Medical Research, China Medical University Hospital, Taichung 404327, Taiwan; School of Chinese Medicine, China Medical University, Taichung, Taiwan; Department of Biotechnology and Bioinformatics, Asia University, Taichung, Taiwan. Electronic address: d0704@mail.cmuh.org.tw.

PMID: 38199299
DOI: 10.1016/j.clim.2024.109897

Abstract

Immunoglobulin E (IgE) synthessis is highly related to a variety of atopic diseases, and several genome-wide association studies (GWASs) have demonstrated the association between genes and IgE level. In this study, we conducted the largest genome-wide association study of IgE involving a Taiwanese Han population. Eight independent variants exhibited genome-wide significance. Among them, an intronic SNP of CD28, rs1181388, and an intergenic SNP, rs1002957030, on 11q23.2 were identified as novel signals for IgE. Seven of the loci were replicated successfully in a meta-analysis using data on Japanese population. Among all the human leukocyte antigen (HLA) regions, HLA-DQA1*03:02 - HLA-DQB1*03:03 was the most significant haplotype (OR = 1.25, SE = 0.02, FDR = 1.6 × 10^-14), corresponding to HLA-DQA1 Asp160 and HLA-DQB1 Leu87 amino acid residues. The genetic correlation showed significance between IgE and allergic diseases including asthma, atopic dermatitis, and pollinosis. IgE PRS was significantly correlated with total IgE levels. Furthermore, the top decile IgE polygenic risk score (PRS) group had the highest risk of asthma for the Taiwan Biobank and Biobank Japan cohorts. IgE PRS may be used to aid in predicting the occurrence of allergic reactions before symptoms occur and biomarkers are detectable. Our study provided a more comprehensive understanding of the impact of genomic variants, including complex HLA alleles, on serum IgE levels.

Keywords: Allergy; genome-wide association study; human leukocyte antigen; immunoglobulin E.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't

MeSH terms

Asthma*
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Hypersensitivity* / genetics
Immunoglobulin E
Polymorphism, Single Nucleotide

Substances

Immunoglobulin E