Novel Signal was identified in the IgE GWAS
The Manhattan plot and QQ plot (λGC:1.05) were shown inFigure 1 . The LDSC demonstrated an intercept of 1.01 (SE, 0.009), and heritability of IgE was 10.7% (SE, 4.1%), which demonstrated the polygenic effect of IgE. After conditional analysis, a total of 8 independent significant loci were identified (Table 2) . The most significant SNP- rs147642819 (6p21.32) was within the intronic region ofHLA-DRA. The intronic SNP of CD28 rs1181388 (p = 2.5×10-12) on 2q33.2 and an intergenic SNP rs1002957030 (p = 4.7×10-8) on 11q23.2 were novel signal for IgE. Six independent signals within chr6 were found included 6p22.1, 6p21.32, and 6q23.3 region (S Figure 2 ). We also identified an intergenic SNP rs112731607 (IL4R; IL21R ) at 16p12.1 as GWAS significance. This region has been reported associated with total serum IgE in a Japanese population as well9. After conducting a meta-analysis with Japanese population (ToMMo), six of the SNPs demonstrated a significant level of association. Among them, rs369358206 within the intergenic region ofHLA-DQA1/HLA-DQB1 is the most significant SNP with pmeta = 1.7×10-23. No increased significance was observed for on chr11 due to lack of SNP results. Although there were no results of lead SNP (rs112731607) in ToMMo for 16q12.1, but another SNP nearby named rs144651842 showed genome-wide significance after meta-analysis (beta=0.18, SE:0.02, pmeta = 9.75×10-17).