The Genome-wide Association Study of Serum IgE Levels Demonstrated the
Shared Genetic Background in Allergic Diseases
Background Immunoglobulin E (IgE) is highly related to a
variety of atopic diseases, and several genome-wide correlation studies
(GWASs) have demonstrated the association between genes and IgE. In this
study, we conducted the largest genome-wide association study of IgE in
a Taiwanese Han population and aimed to elucidate the genetic
architecture of IgE. Methods Genome-wide association study was
used to discover the association between variants and IgE. Through HLA
imputation, we explored the association between HLA alleles and IgE. In
order to explore the pleiotropy relationship between IgE and atopic
diseases, we performed both global and local genetic correlation
analysis. Moreover, we divided our cohort into a training group and a
validation group to construct the polygenic risk score (PRS) of IgE and
applied it to test the risk of asthma and atopic dermatitis.
Results A total of 8 independent variants showed genome-wide
significance, and rs147642819 at 6p21.32 was the most significant signal
(p= 1.8×10 -19). Seven of the loci were replicated
successfully after a meta-analysis of the Japanese population. Among all
the HLA alleles, HLA-DQB1*03:03 is the most significant allele.
The global genetic correlation showed significance between IgE and
asthma. The IgE PRS significantly correlated with the total IgE level.
Furthermore, the top 10 quantile IgE PRS group had a potentially higher
risk for asthma, which was replicated in the Japanese population as
well. Conclusions Our study provided a more comprehensive
understanding of the impact of genomic variants including complex HLA
alleles on serum IgE.