免疫球蛋白E
免疫学
全基因组关联研究
人类白细胞抗原
单倍型
哮喘
人口
生物
连锁不平衡
SNP公司
花粉热
医学
单核苷酸多态性
遗传学
等位基因
基因
基因型
抗原
抗体
环境卫生
作者
Hsing‐Fang Lu,Chen-Hsing Chou,Ying-Ju Lin,Shunsuke Uchiyama,Chikashi Terao,Yuwen Wang,Jai‐Sing Yang,Ting‐Yuan Liu,Henry Sung-Ching Wong,Sean Chun-Chang Chen,Fuu‐Jen Tsai
标识
DOI:10.1016/j.clim.2024.109897
摘要
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.
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