Identification of nine novel loci associated with white blood cell subtypes in a Japanese population.
Identification of nine novel loci associated with white blood cell subtypes in a Japanese population.
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DOI：
10.1371/journal.pgen.1002067
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发表时间：
2011-06
期刊：
影响因子：
4.5
通讯作者：
Kamatani N
中科院分区：
文献类型：
--
作者：
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 FJ;Smith AV;Tanaka T;Couper DJ;Zakai NA;Ferrucci L;Longo DL;Hernandez DG;Witteman JC;Harris TB;O'Donnell CJ;Ganesh SK;Matsuda K;Tsunoda T;Tanaka T;Kubo M;Nakamura Y;Tamari M;Yamamoto K;Kamatani N
白色血细胞（WBC）介导免疫系统，并由具有不同作用的各种亚型组成。阐明调节WBC亚型计数的机制将为免疫系统的病因学和疾病发病机制提供有用的见解。在这项研究中，我们报告了全基因组关联研究（GWAS）的结果，以及对5种主要WBC亚型（中性粒细胞、淋巴细胞、单核细胞、嗜碱性粒细胞和嗜酸性粒细胞）计数的重复研究，使用了14，792名日本受试者，这些受试者参加了BioBank Japan项目。我们确定了12个显著相关的基因座，满足全基因组显著性阈值P<5.0×10−8，其中9个基因座是新的（CDK 6基因座用于中性粒细胞计数; ITGA 4，MLZE，STXBP 6基因座和MHC区域用于单核细胞计数; SLC 45 A3-NUCKS 1，GATA 2，NAALAD 2，ERG基因座用于嗜碱性粒细胞计数）。我们使用15,600名来自高加索人群的受试者进一步评估了已鉴定基因座的相关性。这些WBC亚型相关基因座在WBC亚型内或与总WBC计数、血小板计数或红细胞相关性状（n = 30，454）表现出多种多样的多效性关联模式，这表明这些基因座在造血过程中具有独特和共同的功能作用。 本研究有助于了解白细胞亚型的遗传背景和血液学性状。白色血细胞（WBC）是介导免疫系统并保护身体免受外来微生物侵害的血细胞。众所周知，WBC由具有不同作用的各种细胞亚型组成，尽管尚未检查每种WBC亚型的遗传背景。在这项研究中，我们报告了14,792例日本受试者的5种主要WBC亚型（中性粒细胞、淋巴细胞、单核细胞、嗜碱性粒细胞和嗜酸性粒细胞）的全基因组关联研究（GWAS）。我们确定了12个显著相关的遗传位点，其中9个是新的。在高加索人群队列中对这些确定的基因座的相关性进行评估，证明了WBC亚型的种族共同和不同的遗传背景。这些基因座也表明了多种多样的模式的多效性协会内的血液学性状，包括其他白细胞亚型，总白细胞计数，血小板计数，或红细胞相关的性状，这表明这些基因座在造血过程中的独特和共同的功能作用。
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. White blood cells (WBCs) are blood cells that mediate immune systems and defend the body against foreign microorganisms. It is well known that WBCs consist of various subtypes of cells with distinct roles, although the genetic background of each of the WBC subtypes has yet to be examined. In this study, we report genome-wide association studies (GWAS) for the 5 main WBC subtypes (neutrophils, lymphocytes, monocytes, basophils, and eosinophils) using 14,792 Japanese subjects. We identified 12 significantly associated genetic loci, and 9 of them were novel. Evaluation of the associations of these identified loci in cohorts of Caucasian populations demonstrated both ethnically common and divergent genetic backgrounds of the WBC subtypes. These loci also indicated a variety of patterns of pleiotropic associations within the hematological traits, including the other WBC subtypes, total WBC count, platelet count, or red blood cell-related traits, which suggests unique and common functional roles of these loci in the processes of hematopoiesis.
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影响因子：
30.8
作者：
Chambers, John C.;Zhang, Weihua;Li, Yun;Sehmi, Joban;Wass, Mark N.;Zabaneh, Delilah;Hoggart, Clive;Bayele, Henry;McCarthy, Mark I.;Peltonen, Leena;Freimer, Nelson B.;Srai, Surjit K.;Maxwell, Patrick H.;Sternberg, Michael J. E.;Ruokonen, Aimo;Abecasis, Goncalo;Jarvelin, Marjo-Riitta;Scott, James;Elliott, Paul;Kooner, Jaspal S.
通讯作者：
Kooner, Jaspal S.
影响因子：
5.8
作者：
Johnson, Andrew D.;Handsaker, Robert E.;de Bakker, Paul I. W.
通讯作者：
de Bakker, Paul I. W.
影响因子：
6.8
作者：
Arinobu, Yojiro;Iwasaki, Hiromi;Akashi, Koichi
通讯作者：
Akashi, Koichi
影响因子：
30.5
作者：
Loughran, Stephen J.;Kruse, Elizabeth A.;Kile, Benjamin T.
通讯作者：
Kile, Benjamin T.
影响因子：
30.8
作者：
Gudbjartsson, Daniel F.;Bjornsdottir, Unnur S.;Stefansson, Kari
通讯作者：
Stefansson, Kari