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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)

Author

Listed:
  • 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 III
  • 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 Jr.
  • 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

Abstract

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 16,000 African Americans, we show that, in addition to the previously identified Duffy Antigen Receptor for Chemokines (DARC) locus on chromosome 1, another variant, rs9131, and other nearby variants on human chromosome 4 are associated with total WBC count in African Americans. The variants span the CXCL2 gene, which encodes an inflammatory mediator involved in WBC production and migration. We show that the association is not restricted to African Americans but is also present in independent samples of European Americans, Hispanic Americans, and Japanese. This finding is potentially important because WBC mediate or have altered counts in a variety of acute and chronic disorders.

Suggested Citation

  • 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 , 2011. "Genome-Wide Association Study of White Blood Cell Count in 16,388 African Americans: the Continental Origins and Genetic Epidemiology Network (COGENT)," PLOS Genetics, Public Library of Science, vol. 7(6), pages 1-14, June.
  • Handle: RePEc:plo:pgen00:1002108
    DOI: 10.1371/journal.pgen.1002108
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    References listed on IDEAS

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    1. Nicole Soranzo & Fernando Rivadeneira & Usha Chinappen-Horsley & Ida Malkina & J Brent Richards & Naomi Hammond & Lisette Stolk & Alexandra Nica & Michael Inouye & Albert Hofman & Jonathan Stephens & , 2009. "Meta-Analysis of Genome-Wide Scans for Human Adult Stature Identifies Novel Loci and Associations with Measures of Skeletal Frame Size," PLOS Genetics, Public Library of Science, vol. 5(4), pages 1-13, April.
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    Cited by:

    1. Jonathan D. Mosley & John P. Shelley & Alyson L. Dickson & Jacy Zanussi & Laura L. Daniel & Neil S. Zheng & Lisa Bastarache & Wei-Qi Wei & Mingjian Shi & Gail P. Jarvik & Elisabeth A. Rosenthal & Atla, 2024. "Clinical associations with a polygenic predisposition to benign lower white blood cell counts," Nature Communications, Nature, vol. 15(1), pages 1-12, December.

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