Human Genetics

, Volume 131, Issue 4, pp 639–652

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

  • David R. Crosslin
  • Andrew McDavid
  • Noah Weston
  • Sarah C. Nelson
  • Xiuwen Zheng
  • Eugene Hart
  • Mariza de Andrade
  • Iftikhar J. Kullo
  • Catherine A. McCarty
  • Kimberly F. Doheny
  • Elizabeth Pugh
  • Abel Kho
  • M. Geoffrey Hayes
  • Stephanie Pretel
  • Alexander Saip
  • Marylyn D. Ritchie
  • Dana C. Crawford
  • Paul K. Crane
  • Katherine Newton
  • Rongling Li
  • Daniel B. Mirel
  • Andrew Crenshaw
  • Eric B. Larson
  • Chris S. Carlson
  • Gail P. Jarvik
  • The electronic Medical Records and Genomics (eMERGE) Network
Original Investigation

DOI: 10.1007/s00439-011-1103-9

Cite this article as:
Crosslin, D.R., McDavid, A., Weston, N. et al. Hum Genet (2012) 131: 639. doi:10.1007/s00439-011-1103-9

Abstract

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.

Supplementary material

439_2011_1103_MOESM1_ESM.pdf (622 kb)
Supplementary material 1 (PDF 622 kb)

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • David R. Crosslin
    • 1
    • 4
  • Andrew McDavid
    • 3
  • Noah Weston
    • 2
  • Sarah C. Nelson
    • 4
  • Xiuwen Zheng
    • 4
  • Eugene Hart
    • 2
  • Mariza de Andrade
    • 5
  • Iftikhar J. Kullo
    • 6
  • Catherine A. McCarty
    • 7
  • Kimberly F. Doheny
    • 8
  • Elizabeth Pugh
    • 8
  • Abel Kho
    • 9
  • M. Geoffrey Hayes
    • 10
  • Stephanie Pretel
    • 11
  • Alexander Saip
    • 13
  • Marylyn D. Ritchie
    • 14
  • Dana C. Crawford
    • 12
    • 15
  • Paul K. Crane
    • 16
  • Katherine Newton
    • 2
  • Rongling Li
    • 17
  • Daniel B. Mirel
    • 18
  • Andrew Crenshaw
    • 18
  • Eric B. Larson
    • 2
  • Chris S. Carlson
    • 3
  • Gail P. Jarvik
    • 1
  • The electronic Medical Records and Genomics (eMERGE) Network
  1. 1.Department of Medicine, Division of Medical GeneticsUniversity of WashingtonSeattleUSA
  2. 2.Group Health Research InstituteSeattleUSA
  3. 3.Public Health Sciences DivisionFred Hutchinson Cancer Research CenterSeattleUSA
  4. 4.Department of BiostatisticsUniversity of WashingtonSeattleUSA
  5. 5.Division of Biomedical Statistics and InformaticsMayo ClinicRochesterUSA
  6. 6.Division of Cardiovascular DiseasesMayo ClinicRochesterUSA
  7. 7.Essentia Institute of Rural HealthDuluthUSA
  8. 8.Center for Inherited Disease ResearchJohns Hopkins UniversityBaltimoreUSA
  9. 9.Divisions of General Internal Medicine and Health and Biomedical InformaticsNorthwestern UniversityChicagoUSA
  10. 10.Division of Endocrinology, Metabolism, and Molecular Medicine, Feinberg School of MedicineNorthwestern UniversityChicagoUSA
  11. 11.National Center for Biotechnology InformationNational Library of Medicine, National Institutes of HealthBethesdaUSA
  12. 12.Department of Molecular Physiology and BiophysicsVanderbilt UniversityNashvilleUSA
  13. 13.Vanderbilt Institute for Clinical and Translational ResearchVanderbilt UniversityNashvilleUSA
  14. 14.Department of Biochemistry and Molecular BiologyThe Pennsylvania State UniversityUniversity ParkUSA
  15. 15.Center for Human Genetics ResearchVanderbilt UniversityNashvilleUSA
  16. 16.Department of Medicine, Division of General Internal MedicineUniversity of WashingtonSeattleUSA
  17. 17.Office of Population GenomicsNational Human Genome Research Institute, National Institutes of HealthBethesdaUSA
  18. 18.Program in Medical and Population GeneticsBroad Institute of Harvard and MITCambridgeUSA