Genome-wide association study for levels of total serum IgE identifies HLA-C in a Japanese population

• Published in: PloS one Vol. 8; no. 12; p. e80941
• Main Authors: Yatagai, Yohei, Sakamoto, Tohru, Masuko, Hironori, Kaneko, Yoshiko, Yamada, Hideyasu, Iijima, Hiroaki, Naito, Takashi, Noguchi, Emiko, Hirota, Tomomitsu, Tamari, Mayumi, Imoto, Yoshimasa, Tokunaga, Takahiro, Fujieda, Shigeharu, Konno, Satoshi, Nishimura, Masaharu, Hizawa, Nobuyuki
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 04.12.2013; Public Library of Science (PLoS)
• Subjects: Adult; Adults; Allergies; Analysis; Asian Continental Ancestry Group; Asthma; Asthma - genetics; Asthma - immunology; Chromosomes; Cohort Studies; Dermatitis, Atopic - genetics; Dermatitis, Atopic - immunology; Female; Gene Expression Regulation; Gene loci; Gene mapping; Genetic aspects; Genetic Loci; Genome-wide association studies; Genome-Wide Association Study; Genomes; Genomics; Helper cells; Histocompatibility antigen HLA; HLA antigens; HLA-C Antigens - genetics; HLA-C Antigens - immunology; Humans; Immunoglobulin E; Immunoglobulin E - genetics; Immunoglobulin E - immunology; Laboratories; Loci; Lymphocytes T; Major histocompatibility complex; Male; Medicine; Meta-analysis; Middle Aged; Minority & ethnic groups; Otolaryngology; Polymorphism, Single Nucleotide; Population; Reproducibility; Reproducibility of Results; Respiratory diseases; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Studies; Surgery
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0080941

Most of the previously reported loci for total immunoglobulin E (IgE) levels are related to Th2 cell-dependent pathways. We undertook a genome-wide association study (GWAS) to identify genetic loci responsible for IgE regulation. A total of 479,940 single nucleotide polymorphisms (SNPs) were tested for association with total serum IgE levels in 1180 Japanese adults. Fine-mapping with SNP imputation demonstrated 6 candidate regions: the PYHIN1/IFI16, MHC classes I and II, LEMD2, GRAMD1B, and chr13∶60576338 regions. Replication of these candidate loci in each region was assessed in 2 independent Japanese cohorts (n = 1110 and 1364, respectively). SNP rs3130941 in the HLA-C region was consistently associated with total IgE levels in 3 independent populations, and the meta-analysis yielded genome-wide significance (P = 1.07×10(-10)). Using our GWAS results, we also assessed the reproducibility of previously reported gene associations with total IgE levels. Nine of 32 candidate genes identified by a literature search were associated with total IgE levels after correction for multiple testing. Our findings demonstrate that SNPs in the HLA-C region are strongly associated with total serum IgE levels in the Japanese population and that some of the previously reported genetic associations are replicated across ethnic groups.