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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).

Publication ,  Journal Article
Reiner, AP; Lettre, G; Nalls, MA; Ganesh, SK; Mathias, R; Austin, MA; Dean, E; Arepalli, S; Britton, A; Chen, Z; Couper, D; Curb, JD; Kubo, M ...
Published in: PLoS Genet
June 2011

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.

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Published In

PLoS Genet

DOI

EISSN

1553-7404

Publication Date

June 2011

Volume

7

Issue

6

Start / End Page

e1002108

Location

United States

Related Subject Headings

  • White People
  • Reproducibility of Results
  • Receptors, Cell Surface
  • Polymorphism, Single Nucleotide
  • Phenotype
  • Molecular Epidemiology
  • Microfilament Proteins
  • Leukocyte Count
  • Humans
  • Genome-Wide Association Study
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Reiner, A. P., Lettre, G., Nalls, M. A., Ganesh, S. K., Mathias, R., Austin, M. A., … Wilson, J. G. (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, 7(6). https://doi.org/10.1371/journal.pgen.1002108
Reiner, A. P., G. Lettre, M. A. Nalls, S. K. Ganesh, R. Mathias, M. A. Austin, E. Dean, et al. “Genome-Wide association study of white blood cell count in 16,388 african americans: The continental Origins and Genetic Epidemiology network (COGENT).” PLoS Genetics 7, no. 6 (2011). https://doi.org/10.1371/journal.pgen.1002108.
Reiner, A. P., et al. “Genome-Wide association study of white blood cell count in 16,388 african americans: The continental Origins and Genetic Epidemiology network (COGENT).” PLoS Genetics, vol. 7, no. 6, 2011. Manual, doi:10.1371/journal.pgen.1002108.
Reiner AP, Lettre G, Nalls MA, Ganesh SK, Mathias R, Austin MA, Dean E, Arepalli S, Britton A, Chen Z, Couper D, Curb JD, Eaton CB, Fornage M, Grant SFA, Harris TB, Hernandez D, Kamatini N, Keating BJ, Kubo M, LaCroix A, Lange LA, Liu S, Lohman K, Meng Y, Mohler ER, Musani S, Nakamura Y, O’Donnell CJ, Okada Y, Palmer CD, Papanicolaou GJ, Patel KV, Singleton AB, Takahashi A, Tang H, Taylor Jr. HA, Taylor K, Thomson C, Yanek LR, Yang L, Ziv E, Zonderman AB, Folsom AR, Evans MK, Liu Y, Becker DM, Snively BM, Wilson JG. Genome-Wide association study of white blood cell count in 16,388 african americans: The continental Origins and Genetic Epidemiology network (COGENT). PLoS Genetics. 2011;7(6).

Published In

PLoS Genet

DOI

EISSN

1553-7404

Publication Date

June 2011

Volume

7

Issue

6

Start / End Page

e1002108

Location

United States

Related Subject Headings

  • White People
  • Reproducibility of Results
  • Receptors, Cell Surface
  • Polymorphism, Single Nucleotide
  • Phenotype
  • Molecular Epidemiology
  • Microfilament Proteins
  • Leukocyte Count
  • Humans
  • Genome-Wide Association Study