title: Genome-wide association study for levels of total serum IgE identifies HLA-C in a Japanese population.
abstract: 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.
authors: Department of Pulmonary Medicine, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
authors: Yohei
authors: Y
authors: Yatagai
authors: Tohru
authors: T
authors: Sakamoto
authors: Hironori
authors: H
authors: Masuko
authors: Yoshiko
authors: Y
authors: Kaneko
authors: Hideyasu
authors: H
authors: Yamada
authors: Hiroaki
authors: H
authors: Iijima
authors: Takashi
authors: T
authors: Naito
authors: Emiko
authors: E
authors: Noguchi
authors: Tomomitsu
authors: T
authors: Hirota
authors: Mayumi
authors: M
authors: Tamari
authors: Yoshimasa
authors: Y
authors: Imoto
authors: Takahiro
authors: T
authors: Tokunaga
authors: Shigeharu
authors: S
authors: Fujieda
authors: Satoshi
authors: S
authors: Konno
authors: Masaharu
authors: M
authors: Nishimura
authors: Nobuyuki
authors: N
authors: Hizawa
mesh_terms: D000328:Adult; D044466:Asian People; D001249:Asthma / Q000235:genetics* / Q000276:immunology; D015331:Cohort Studies; D003876:Dermatitis, Atopic / Q000235:genetics* / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D015236:HLA-C Antigens / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007073:Immunoglobulin E / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results
chemical_list: D015236:HLA-C Antigens; D007073:Immunoglobulin E