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 journalArticle

50 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 - 01-06-2011

Fingerprint

leukocytes
Leukocytes
blood
loci
Basophils
Population
Leukocyte Count
Monocytes
Neutrophils
basophils
immune system
leukocyte count
monocytes
Genome-Wide Association Study
Immune System Diseases
Hematopoiesis
neutrophils
Platelet Count
Eosinophils
genome

All Science Journal Classification (ASJC) codes

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

Cite this

Okada, Y., Hirota, T., Kamatani, Y., Takahashi, A., Ohmiya, H., Kumasaka, N., ... Kamatani, N. (2011). Identification of nine novel loci associated with white blood cell subtypes in a Japanese population. PLoS Genetics, 7(6), [e1002067]. https://doi.org/10.1371/journal.pgen.1002067
Okada, Yukinori ; Hirota, Tomomitsu ; Kamatani, Yoichiro ; Takahashi, Atsushi ; Ohmiya, Hiroko ; Kumasaka, Natsuhiko ; Higasa, Koichiro ; Yamaguchi-Kabata, Yumi ; Hosono, Naoya ; Nalls, Michael A. ; Chen, Ming Huei ; van Rooij, Frank J.A. ; Smith, Albert V. ; Tanaka, Toshiko ; Couper, David J. ; Zakai, Neil A. ; Ferrucci, Luigi ; Longo, Dan L. ; Hernandez, Dena G. ; Witteman, Jacqueline C.M. ; Harris, Tamara B. ; O'Donnell, Christopher J. ; Ganesh, Santhi K. ; Matsuda, Koichi ; Tsunoda, Tatsuhiko ; Tanaka, Toshihiro ; Kubo, Michiaki ; Nakamura, Yusuke ; Tamari, Mayumi ; Yamamoto, Kazuhiko ; Kamatani, Naoyuki. / Identification of nine novel loci associated with white blood cell subtypes in a Japanese population. In: PLoS Genetics. 2011 ; Vol. 7, No. 6.
@article{27059c28fbea44a98ada4a9a34cf2836,
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.",
author = "Yukinori Okada and Tomomitsu Hirota and Yoichiro Kamatani and Atsushi Takahashi and Hiroko Ohmiya and Natsuhiko Kumasaka and Koichiro Higasa and Yumi Yamaguchi-Kabata and Naoya Hosono and Nalls, {Michael A.} and Chen, {Ming Huei} and {van Rooij}, {Frank J.A.} and Smith, {Albert V.} and Toshiko Tanaka and Couper, {David J.} and Zakai, {Neil A.} and Luigi Ferrucci and Longo, {Dan L.} and Hernandez, {Dena G.} and Witteman, {Jacqueline C.M.} and Harris, {Tamara B.} and O'Donnell, {Christopher J.} and Ganesh, {Santhi K.} and Koichi Matsuda and Tatsuhiko Tsunoda and Toshihiro Tanaka and Michiaki Kubo and Yusuke Nakamura and Mayumi Tamari and Kazuhiko Yamamoto and Naoyuki Kamatani",
year = "2011",
month = "6",
day = "1",
doi = "10.1371/journal.pgen.1002067",
language = "English",
volume = "7",
journal = "PLoS Genetics",
issn = "1553-7390",
publisher = "Public Library of Science",
number = "6",

}

Okada, Y, Hirota, T, Kamatani, Y, Takahashi, A, Ohmiya, H, Kumasaka, N, Higasa, K, Yamaguchi-Kabata, Y, Hosono, N, Nalls, MA, Chen, MH, van Rooij, FJA, Smith, AV, Tanaka, T, Couper, DJ, Zakai, NA, Ferrucci, L, Longo, DL, Hernandez, DG, Witteman, JCM, Harris, TB, O'Donnell, CJ, Ganesh, SK, Matsuda, K, Tsunoda, T, Tanaka, T, Kubo, M, Nakamura, Y, Tamari, M, Yamamoto, K & Kamatani, N 2011, 'Identification of nine novel loci associated with white blood cell subtypes in a Japanese population', PLoS Genetics, vol. 7, no. 6, e1002067. https://doi.org/10.1371/journal.pgen.1002067

Identification of nine novel loci associated with white blood cell subtypes in a Japanese population. / Okada, Yukinori; Hirota, Tomomitsu; Kamatani, Yoichiro; Takahashi, Atsushi; Ohmiya, Hiroko; Kumasaka, Natsuhiko; Higasa, Koichiro; Yamaguchi-Kabata, Yumi; Hosono, Naoya; Nalls, Michael A.; Chen, Ming Huei; van Rooij, Frank J.A.; Smith, Albert V.; Tanaka, Toshiko; Couper, David J.; Zakai, Neil A.; Ferrucci, Luigi; Longo, Dan L.; Hernandez, Dena G.; Witteman, Jacqueline C.M.; Harris, Tamara B.; O'Donnell, Christopher J.; Ganesh, Santhi K.; Matsuda, Koichi; Tsunoda, Tatsuhiko; Tanaka, Toshihiro; Kubo, Michiaki; Nakamura, Yusuke; Tamari, Mayumi; Yamamoto, Kazuhiko; Kamatani, Naoyuki.

In: PLoS Genetics, Vol. 7, No. 6, e1002067, 01.06.2011.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Identification of nine novel loci associated with white blood cell subtypes in a Japanese population

AU - Okada, Yukinori

AU - Hirota, Tomomitsu

AU - Kamatani, Yoichiro

AU - Takahashi, Atsushi

AU - Ohmiya, Hiroko

AU - Kumasaka, Natsuhiko

AU - Higasa, Koichiro

AU - Yamaguchi-Kabata, Yumi

AU - Hosono, Naoya

AU - Nalls, Michael A.

AU - Chen, Ming Huei

AU - van Rooij, Frank J.A.

AU - Smith, Albert V.

AU - Tanaka, Toshiko

AU - Couper, David J.

AU - Zakai, Neil A.

AU - Ferrucci, Luigi

AU - Longo, Dan L.

AU - Hernandez, Dena G.

AU - Witteman, Jacqueline C.M.

AU - Harris, Tamara B.

AU - O'Donnell, Christopher J.

AU - Ganesh, Santhi K.

AU - Matsuda, Koichi

AU - Tsunoda, Tatsuhiko

AU - Tanaka, Toshihiro

AU - Kubo, Michiaki

AU - Nakamura, Yusuke

AU - Tamari, Mayumi

AU - Yamamoto, Kazuhiko

AU - Kamatani, Naoyuki

PY - 2011/6/1

Y1 - 2011/6/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=79959859184&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79959859184&partnerID=8YFLogxK

U2 - 10.1371/journal.pgen.1002067

DO - 10.1371/journal.pgen.1002067

M3 - Article

C2 - 21738478

AN - SCOPUS:79959859184

VL - 7

JO - PLoS Genetics

JF - PLoS Genetics

SN - 1553-7390

IS - 6

M1 - e1002067

ER -