Genome-Wide Association Study for Levels of Total Serum IgE Identifies HLA-C in a Japanese Population

Yohei Yatagai, Tohru Sakamoto, Hironori Masuko, Yoshiko Kaneko, Hideyasu Yamada, Hiroaki Iijima, Takashi Naito, Emiko Noguchi, Tomomitsu Hirota, Mayumi Tamari, Yoshimasa Imoto, Takahiro Tokunaga, Shigeharu Fujieda, Satoshi Konno, Masaharu Nishimura and Nobuyuki Hizawa

PLOS ONE, 2013, vol. 8, issue 12, 1-9

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.

Date: 2013
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0080941

DOI: 10.1371/journal.pone.0080941

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