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
Y1 - 2011/6
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.
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U2 - 10.1371/journal.pgen.1002067
DO - 10.1371/journal.pgen.1002067
M3 - Article
C2 - 21738478
AN - SCOPUS:79959859184
SN - 1553-7390
VL - 7
JO - PLoS Genetics
JF - PLoS Genetics
IS - 6
M1 - e1002067
ER -
