Genetic variants associated with the white blood cell count in 13,923 subjects in the eMERGE Network

Hum Genet. 2012 Apr;131(4):639-52. doi: 10.1007/s00439-011-1103-9. Epub 2011 Oct 30.


White blood cell count (WBC) is unique among identified inflammatory predictors of chronic disease in that it is routinely measured in asymptomatic patients in the course of routine patient care. We led a genome-wide association analysis to identify variants associated with WBC levels in 13,923 subjects in the electronic Medical Records and Genomics (eMERGE) Network. We identified two regions of interest that were each unique to subjects of genetically determined ancestry to the African continent (AA) or to the European continent (EA). WBC varies among different ancestry groups. Despite being ancestry specific, these regions were identifiable in the combined analysis. In AA subjects, the region surrounding the Duffy antigen/chemokine receptor gene (DARC) on 1q21 exhibited significant association (p value = 6.71e-55). These results validate the previously reported association between WBC and of the regulatory variant rs2814778 in the promoter region, which causes the Duffy negative phenotype (Fy-/-). A second missense variant (rs12075) is responsible for the two principal antigens, Fya and Fyb of the Duffy blood group system. The two variants, consisting of four alleles, act in concert to produce five antigens and subsequent phenotypes. We were able to identify the marginal and novel interaction effects of these two variants on WBC. In the EA subjects, we identified significantly associated SNPs tagging three separate genes in the 17q21 region: (1) GSDMA, (2) MED24, and (3) PSMD3. Variants in this region have been reported to be associated with WBC, neutrophil count, and inflammatory diseases including asthma and Crohn's disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Black People / genetics
  • Duffy Blood-Group System / genetics
  • Female
  • Gene Frequency
  • Genetic Variation*
  • Genome, Human / genetics
  • Genome-Wide Association Study / methods*
  • Genome-Wide Association Study / statistics & numerical data
  • Genotype
  • Humans
  • Leukocyte Count*
  • Male
  • Mediator Complex / genetics
  • Medical Records / statistics & numerical data
  • Middle Aged
  • Neoplasm Proteins / genetics
  • Polymorphism, Single Nucleotide
  • Principal Component Analysis
  • Proteasome Endopeptidase Complex / genetics
  • Receptors, Cell Surface / genetics
  • White People / genetics
  • White People / statistics & numerical data


  • ACKR1 protein, human
  • Duffy Blood-Group System
  • GSDMA protein, human
  • MED24 protein, human
  • Mediator Complex
  • Neoplasm Proteins
  • Receptors, Cell Surface
  • Proteasome Endopeptidase Complex
  • proteasome activator PA700 subunit p58, human