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

Author

Listed:
  • 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
  • Nobuyuki Hizawa

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.

Suggested Citation

  • Yohei Yatagai & Tohru Sakamoto & Hironori Masuko & Yoshiko Kaneko & Hideyasu Yamada & Hiroaki Iijima & Takashi Naito & Emiko Noguchi & Tomomitsu Hirota & Mayumi Tamari & Yoshimasa Imoto & Takahiro Tok, 2013. "Genome-Wide Association Study for Levels of Total Serum IgE Identifies HLA-C in a Japanese Population," PLOS ONE, Public Library of Science, vol. 8(12), pages 1-9, December.
    • Handle: RePEc:plo:pone00:0080941
    DOI: 10.1371/journal.pone.0080941
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    1. Indra Adrianto & Chee Paul Lin & Jessica J Hale & Albert M Levin & Indrani Datta & Ryan Parker & Adam Adler & Jennifer A Kelly & Kenneth M Kaufman & Christopher J Lessard & Kathy L Moser & Robert P Ki, 2012. "Genome-Wide Association Study of African and European Americans Implicates Multiple Shared and Ethnic Specific Loci in Sarcoidosis Susceptibility," PLOS ONE, Public Library of Science, vol. 7(8), pages 1-10, August.
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