Genome-wide association study of white blood cell count in 16,388 African Americans: the continental origins and genetic epidemiology network (COGENT).

Total white blood cell (WBC) and neutrophil counts are lower among individuals of African descent due to the common African-derived "null" variant of the Duffy Antigen Receptor for Chemokines (DARC) gene. Additional common genetic polymorphisms were recently associated with total WBC and W...

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Autores principales:	Alexander P Reiner, Guillaume Lettre, Michael A Nalls, Santhi K Ganesh, Rasika Mathias, Melissa A Austin, Eric Dean, Sampath Arepalli, Angela Britton, Zhao Chen, David Couper, J David Curb, Charles B Eaton, Myriam Fornage, Struan F A Grant, Tamara B Harris, Dena Hernandez, Naoyuki Kamatini, Brendan J Keating, Michiaki Kubo, Andrea LaCroix, Leslie A Lange, Simin Liu, Kurt Lohman, Yan Meng, Emile R Mohler, Solomon Musani, Yusuke Nakamura, Christopher J O'Donnell, Yukinori Okada, Cameron D Palmer, George J Papanicolaou, Kushang V Patel, Andrew B Singleton, Atsushi Takahashi, Hua Tang, Herman A Taylor, Kent Taylor, Cynthia Thomson, Lisa R Yanek, Lingyao Yang, Elad Ziv, Alan B Zonderman, Aaron R Folsom, Michele K Evans, Yongmei Liu, Diane M Becker, Beverly M Snively, James G Wilson
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/fa73d81adc4140c4b34a3fad239f6ba6
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spelling	oai:doaj.org-article:fa73d81adc4140c4b34a3fad239f6ba62021-11-18T06:17:17ZGenome-wide association study of white blood cell count in 16,388 African Americans: the continental origins and genetic epidemiology network (COGENT).1553-73901553-740410.1371/journal.pgen.1002108https://doaj.org/article/fa73d81adc4140c4b34a3fad239f6ba62011-06-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21738479/?tool=EBIhttps://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404Total white blood cell (WBC) and neutrophil counts are lower among individuals of African descent due to the common African-derived "null" variant of the Duffy Antigen Receptor for Chemokines (DARC) gene. Additional common genetic polymorphisms were recently associated with total WBC and WBC sub-type levels in European and Japanese populations. No additional loci that account for WBC variability have been identified in African Americans. In order to address this, we performed a large genome-wide association study (GWAS) of total WBC and cell subtype counts in 16,388 African-American participants from 7 population-based cohorts available in the Continental Origins and Genetic Epidemiology Network. In addition to the DARC locus on chromosome 1q23, we identified two other regions (chromosomes 4q13 and 16q22) associated with WBC in African Americans (P<2.5×10(-8)). The lead SNP (rs9131) on chromosome 4q13 is located in the CXCL2 gene, which encodes a chemotactic cytokine for polymorphonuclear leukocytes. Independent evidence of the novel CXCL2 association with WBC was present in 3,551 Hispanic Americans, 14,767 Japanese, and 19,509 European Americans. The index SNP (rs12149261) on chromosome 16q22 associated with WBC count is located in a large inter-chromosomal segmental duplication encompassing part of the hydrocephalus inducing homolog (HYDIN) gene. We demonstrate that the chromosome 16q22 association finding is most likely due to a genotyping artifact as a consequence of sequence similarity between duplicated regions on chromosomes 16q22 and 1q21. Among the WBC loci recently identified in European or Japanese populations, replication was observed in our African-American meta-analysis for rs445 of CDK6 on chromosome 7q21 and rs4065321 of PSMD3-CSF3 region on chromosome 17q21. In summary, the CXCL2, CDK6, and PSMD3-CSF3 regions are associated with WBC count in African American and other populations. We also demonstrate that large inter-chromosomal duplications can result in false positive associations in GWAS.Alexander P ReinerGuillaume LettreMichael A NallsSanthi K GaneshRasika MathiasMelissa A AustinEric DeanSampath ArepalliAngela BrittonZhao ChenDavid CouperJ David CurbCharles B EatonMyriam FornageStruan F A GrantTamara B HarrisDena HernandezNaoyuki KamatiniBrendan J KeatingMichiaki KuboAndrea LaCroixLeslie A LangeSimin LiuKurt LohmanYan MengEmile R MohlerSolomon MusaniYusuke NakamuraChristopher J O'DonnellYukinori OkadaCameron D PalmerGeorge J PapanicolaouKushang V PatelAndrew B SingletonAtsushi TakahashiHua TangHerman A TaylorKent TaylorCynthia ThomsonLisa R YanekLingyao YangElad ZivAlan B ZondermanAaron R FolsomMichele K EvansYongmei LiuDiane M BeckerBeverly M SnivelyJames G WilsonPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 7, Iss 6, p e1002108 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 Alexander P Reiner Guillaume Lettre Michael A Nalls Santhi K Ganesh Rasika Mathias Melissa A Austin Eric Dean Sampath Arepalli Angela Britton Zhao Chen David Couper J David Curb Charles B Eaton Myriam Fornage Struan F A Grant Tamara B Harris Dena Hernandez Naoyuki Kamatini Brendan J Keating Michiaki Kubo Andrea LaCroix Leslie A Lange Simin Liu Kurt Lohman Yan Meng Emile R Mohler Solomon Musani Yusuke Nakamura Christopher J O'Donnell Yukinori Okada Cameron D Palmer George J Papanicolaou Kushang V Patel Andrew B Singleton Atsushi Takahashi Hua Tang Herman A Taylor Kent Taylor Cynthia Thomson Lisa R Yanek Lingyao Yang Elad Ziv Alan B Zonderman Aaron R Folsom Michele K Evans Yongmei Liu Diane M Becker Beverly M Snively James G Wilson Genome-wide association study of white blood cell count in 16,388 African Americans: the continental origins and genetic epidemiology network (COGENT).
description	Total white blood cell (WBC) and neutrophil counts are lower among individuals of African descent due to the common African-derived "null" variant of the Duffy Antigen Receptor for Chemokines (DARC) gene. Additional common genetic polymorphisms were recently associated with total WBC and WBC sub-type levels in European and Japanese populations. No additional loci that account for WBC variability have been identified in African Americans. In order to address this, we performed a large genome-wide association study (GWAS) of total WBC and cell subtype counts in 16,388 African-American participants from 7 population-based cohorts available in the Continental Origins and Genetic Epidemiology Network. In addition to the DARC locus on chromosome 1q23, we identified two other regions (chromosomes 4q13 and 16q22) associated with WBC in African Americans (P<2.5×10(-8)). The lead SNP (rs9131) on chromosome 4q13 is located in the CXCL2 gene, which encodes a chemotactic cytokine for polymorphonuclear leukocytes. Independent evidence of the novel CXCL2 association with WBC was present in 3,551 Hispanic Americans, 14,767 Japanese, and 19,509 European Americans. The index SNP (rs12149261) on chromosome 16q22 associated with WBC count is located in a large inter-chromosomal segmental duplication encompassing part of the hydrocephalus inducing homolog (HYDIN) gene. We demonstrate that the chromosome 16q22 association finding is most likely due to a genotyping artifact as a consequence of sequence similarity between duplicated regions on chromosomes 16q22 and 1q21. Among the WBC loci recently identified in European or Japanese populations, replication was observed in our African-American meta-analysis for rs445 of CDK6 on chromosome 7q21 and rs4065321 of PSMD3-CSF3 region on chromosome 17q21. In summary, the CXCL2, CDK6, and PSMD3-CSF3 regions are associated with WBC count in African American and other populations. We also demonstrate that large inter-chromosomal duplications can result in false positive associations in GWAS.
format	article
author	Alexander P Reiner Guillaume Lettre Michael A Nalls Santhi K Ganesh Rasika Mathias Melissa A Austin Eric Dean Sampath Arepalli Angela Britton Zhao Chen David Couper J David Curb Charles B Eaton Myriam Fornage Struan F A Grant Tamara B Harris Dena Hernandez Naoyuki Kamatini Brendan J Keating Michiaki Kubo Andrea LaCroix Leslie A Lange Simin Liu Kurt Lohman Yan Meng Emile R Mohler Solomon Musani Yusuke Nakamura Christopher J O'Donnell Yukinori Okada Cameron D Palmer George J Papanicolaou Kushang V Patel Andrew B Singleton Atsushi Takahashi Hua Tang Herman A Taylor Kent Taylor Cynthia Thomson Lisa R Yanek Lingyao Yang Elad Ziv Alan B Zonderman Aaron R Folsom Michele K Evans Yongmei Liu Diane M Becker Beverly M Snively James G Wilson
author_facet	Alexander P Reiner Guillaume Lettre Michael A Nalls Santhi K Ganesh Rasika Mathias Melissa A Austin Eric Dean Sampath Arepalli Angela Britton Zhao Chen David Couper J David Curb Charles B Eaton Myriam Fornage Struan F A Grant Tamara B Harris Dena Hernandez Naoyuki Kamatini Brendan J Keating Michiaki Kubo Andrea LaCroix Leslie A Lange Simin Liu Kurt Lohman Yan Meng Emile R Mohler Solomon Musani Yusuke Nakamura Christopher J O'Donnell Yukinori Okada Cameron D Palmer George J Papanicolaou Kushang V Patel Andrew B Singleton Atsushi Takahashi Hua Tang Herman A Taylor Kent Taylor Cynthia Thomson Lisa R Yanek Lingyao Yang Elad Ziv Alan B Zonderman Aaron R Folsom Michele K Evans Yongmei Liu Diane M Becker Beverly M Snively James G Wilson
author_sort	Alexander P Reiner
title	Genome-wide association study of white blood cell count in 16,388 African Americans: the continental origins and genetic epidemiology network (COGENT).
title_short	Genome-wide association study of white blood cell count in 16,388 African Americans: the continental origins and genetic epidemiology network (COGENT).
title_full	Genome-wide association study of white blood cell count in 16,388 African Americans: the continental origins and genetic epidemiology network (COGENT).
title_fullStr	Genome-wide association study of white blood cell count in 16,388 African Americans: the continental origins and genetic epidemiology network (COGENT).
title_full_unstemmed	Genome-wide association study of white blood cell count in 16,388 African Americans: the continental origins and genetic epidemiology network (COGENT).
title_sort	genome-wide association study of white blood cell count in 16,388 african americans: the continental origins and genetic epidemiology network (cogent).
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/fa73d81adc4140c4b34a3fad239f6ba6
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Genome-wide association study of white blood cell count in 16,388 African Americans: the continental origins and genetic epidemiology network (COGENT).

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