Identification of nine novel loci associated with white blood cell subtypes in a Japanese population

Yukinori Okada, Tomomitsu Hirota, Yoichiro Kamatani, Atsushi Takahashi, Hiroko Ohmiya, Natsuhiko Kumasaka, Koichiro Higasa, Yumi Yamaguchi-Kabata, Naoya Hosono, Michael A. Nalls, Ming Huei Chen, Frank J.A. van Rooij, Albert V. Smith, Toshiko Tanaka, David J. Couper, Neil A. Zakai, Luigi Ferrucci, Dan L. Longo, Dena G. Hernandez, Jacqueline C.M. WittemanTamara B. Harris, Christopher J. O'Donnell, Santhi K. Ganesh, Koichi Matsuda, Tatsuhiko Tsunoda, Toshihiro Tanaka, Michiaki Kubo, Yusuke Nakamura, Mayumi Tamari, Kazuhiko Yamamoto, Naoyuki Kamatani

Research output: Contribution to journalArticlepeer-review

52 Citations (Scopus)

Abstract

White blood cells (WBCs) mediate immune systems and consist of various subtypes with distinct roles. Elucidation of the mechanism that regulates the counts of the WBC subtypes would provide useful insights into both the etiology of the immune system and disease pathogenesis. In this study, we report results of genome-wide association studies (GWAS) and a replication study for the counts of the 5 main WBC subtypes (neutrophils, lymphocytes, monocytes, basophils, and eosinophils) using 14,792 Japanese subjects enrolled in the BioBank Japan Project. We identified 12 significantly associated loci that satisfied the genome-wide significance threshold of P<5.0×10-8, of which 9 loci were novel (the CDK6 locus for the neutrophil count; the ITGA4, MLZE, STXBP6 loci, and the MHC region for the monocyte count; the SLC45A3-NUCKS1, GATA2, NAALAD2, ERG loci for the basophil count). We further evaluated associations in the identified loci using 15,600 subjects from Caucasian populations. These WBC subtype-related loci demonstrated a variety of patterns of pleiotropic associations within the WBC subtypes, or with total WBC count, platelet count, or red blood cell-related traits (n = 30,454), which suggests unique and common functional roles of these loci in the processes of hematopoiesis. This study should contribute to the understanding of the genetic backgrounds of the WBC subtypes and hematological traits.

Original languageEnglish
Article numbere1002067
JournalPLoS Genetics
Volume7
Issue number6
DOIs
Publication statusPublished - 2011 Jun

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

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