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Identification of nine novel loci associated with white blood cell subtypes in a Japanese population
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نویسنده
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okada y. ,hirota t. ,kamatani y. ,takahashi a. ,ohmiya h. ,kumasaka n. ,higasa k. ,yamaguchi-kabata y. ,hosono n. ,nalls m.a. ,chen m.h. ,van rooij f.j.a. ,smith a.v. ,tanaka t. ,couper d.j. ,zakai n.a. ,ferrucci l. ,longo d.l. ,hernandez d.g. ,witteman j.c.m. ,harris t.b. ,o'donnell c.j. ,ganesh s.k. ,matsuda k. ,tsunoda t. ,tanaka t. ,kubo m. ,nakamura y. ,tamari m. ,yamamoto k. ,kamatani n.
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منبع
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plos genetics - 2011 - دوره : 7 - شماره : 6
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چکیده
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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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آدرس
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laboratory for statistical analysis,center for genomic medicine (cgm),institute of physical and chemical research (riken),yokohama,japan,department of allergy and rheumatology,graduate school of medicine,university of tokyo,tokyo, Japan, laboratory for respiratory diseases,center for genomic medicine,institute of physical and chemical research,yokohama, Japan, centre d'etude du polymorphisme humain (ceph),paris, France, laboratory for statistical analysis,center for genomic medicine (cgm),institute of physical and chemical research (riken),yokohama, Japan, laboratory for statistical analysis,center for genomic medicine (cgm),institute of physical and chemical research (riken),yokohama, Japan, laboratory for statistical analysis,center for genomic medicine (cgm),institute of physical and chemical research (riken),yokohama, Japan, laboratory for statistical analysis,center for genomic medicine (cgm),institute of physical and chemical research (riken),yokohama, Japan, laboratory for statistical analysis,center for genomic medicine (cgm),institute of physical and chemical research (riken),yokohama, Japan, laboratory for genotyping development,center for genomic medicine,institute of physical and chemical research,yokohama, Japan, laboratory of neurogenetics,national institute on aging,national institutes of health,baltimore,md, United States, national heart,lung,and blood institute's (nhlbi),framingham heart study,framingham,ma,united states,department of neurology,boston university school of medicine,boston,ma, United States, department of epidemiology,erasmus mc,rotterdam,netherlands,netherlands consortium for healthy aging (ngincha),the netherlands genomics initiative,leiden, Netherlands, icelandic heart association,kopavogur, Iceland, longitudinal studies section,clinical research branch,national institute on aging,national institutes of health,baltimore,ma, United States, collaborative studies coordinating center,department of biostatistics,the university of north carolina at chapel hill,chapel hill,nc, United States, department of medicine,university of vermont college of medicine,burlington,vt, United States, longitudinal studies section,clinical research branch,national institute on aging,national institutes of health,baltimore,ma, United States, clinical research branch,national institute on aging,national institutes of health,baltimore,ma, United States, laboratory of neurogenetics,national institute on aging,national institutes of health,baltimore,md, United States, department of epidemiology,erasmus mc,rotterdam,netherlands,netherlands consortium for healthy aging (ngincha),the netherlands genomics initiative,leiden, Netherlands, laboratory for epidemiology,demography,and biometry,national institute on aging,national institutes of health,baltimore,ma, United States, national heart,lung,and blood institute's (nhlbi),framingham heart study,framingham,ma,united states,division of intramural research,national heart,lung,and blood institute,bethesda,ma, United States, division of cardiovascular medicine,department of internal medicine,university of michigan,ann arbor,mi, United States, laboratory of molecular medicine,human genome center,institute of medical science,university of tokyo,tokyo, Japan, laboratory for medical informatics,center for genomic medicine,institute of physical and chemical research,yokohama, Japan, laboratory for cardiovascular diseases,center for genomic medicine,institute of physical and chemical research,yokohama, Japan, laboratory for genotyping development,center for genomic medicine,institute of physical and chemical research,yokohama, Japan, laboratory of molecular medicine,human genome center,institute of medical science,university of tokyo,tokyo, Japan, laboratory for respiratory diseases,center for genomic medicine,institute of physical and chemical research,yokohama, Japan, department of allergy and rheumatology,graduate school of medicine,university of tokyo,tokyo, Japan, laboratory for statistical analysis,center for genomic medicine (cgm),institute of physical and chemical research (riken),yokohama, Japan
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Authors
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