Among allergic diseases, atopic dermatitis, asthma, hay fever, and urticarial have achieved excellent results for the development of biologics such as omalizumab and dupilumab. The scientific basis for disease and biologics is often supported by disease gene cohort studies centered on genome-wide association studies (GWASes). Immunoglobulin E (IgE), which is produced mainly in plasma cells, plays a crucial role in immune functions and is related to Th2 cell-mediated allergic inflammatory

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... s such as atopic dermatitis, asthma, and allergic rhinitis. Studies of twin and family samples ascertained through atopic disease reported that genetic factors are important for total IgE levels and account for 45% to 78% heritability of its levels. GWASes for total IgE levels have showed that polymorphisms in IL4R, STAT6, FCER1A, the IL13/RAD50, TSLP locus and the major histocompatibility complex (MHC) are associated with total IgE concentrations in European, African, and Japanese on a scale of 10,000 individuals, but the results vary among ethnic groups and regions. We thus far reported associated locus around the IL4R gene in a GWAS using about 10,000 individuals, but we expected that there still exist hidden loci associated with total serum IgE levels which will be revealed by GWASes with more study samples. In this report, we show the results of a GWAS with a new dataset expanded to about 60,000 Japanese individuals in Miyagi (7,300 km2) or Iwate (15,300 km2) prefectures. Since individuals in our dataset are from such neighboring limited areas, both of which are smaller than Sardinia (24,000 km2), less regional and ethnic biases are expected. As a result of performing the world's largest GWAS, we identified 45 associated loci in the discovery set and 22 of them were replicated. Of the 22 replicated loci, MHC region showed the strongest association.