title: Identification of nine novel loci associated with white blood cell subtypes in a Japanese population.
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.
authors: Laboratory for Statistical Analysis, Center for Genomic Medicine, Institute of Physical and Chemical Research, Yokohama, Japan. yokada@src.riken.jp
authors: Yukinori
authors: Y
authors: Okada
authors: Tomomitsu
authors: T
authors: Hirota
authors: Yoichiro
authors: Y
authors: Kamatani
authors: Atsushi
authors: A
authors: Takahashi
authors: Hiroko
authors: H
authors: Ohmiya
authors: Natsuhiko
authors: N
authors: Kumasaka
authors: Koichiro
authors: K
authors: Higasa
authors: Yumi
authors: Y
authors: Yamaguchi-Kabata
authors: Naoya
authors: N
authors: Hosono
authors: Michael A
authors: MA
authors: Nalls
authors: Ming Huei
authors: MH
authors: Chen
authors: Frank J A
authors: FJ
authors: van Rooij
authors: Albert V
authors: AV
authors: Smith
authors: Toshiko
authors: T
authors: Tanaka
authors: David J
authors: DJ
authors: Couper
authors: Neil A
authors: NA
authors: Zakai
authors: Luigi
authors: L
authors: Ferrucci
authors: Dan L
authors: DL
authors: Longo
authors: Dena G
authors: DG
authors: Hernandez
authors: Jacqueline C M
authors: JC
authors: Witteman
authors: Tamara B
authors: TB
authors: Harris
authors: Christopher J
authors: CJ
authors: O'Donnell
authors: Santhi K
authors: SK
authors: Ganesh
authors: Koichi
authors: K
authors: Matsuda
authors: Tatsuhiko
authors: T
authors: Tsunoda
authors: Toshihiro
authors: T
authors: Tanaka
authors: Michiaki
authors: M
authors: Kubo
authors: Yusuke
authors: Y
authors: Nakamura
authors: Mayumi
authors: M
authors: Tamari
authors: Kazuhiko
authors: K
authors: Yamamoto
authors: Naoyuki
authors: N
authors: Kamatani
mesh_terms: D044466:Asian People / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D056426:Genetic Loci / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D044465:White People / Q000235:genetics