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. 2008 Jan;82(1):81-7.
doi: 10.1016/j.ajhg.2007.09.003.

Admixture mapping of white cell count: genetic locus responsible for lower white blood cell count in the Health ABC and Jackson Heart studies

Michael A Nalls  1 , James G Wilson, Nick J Patterson, Arti Tandon, Joseph M Zmuda, Scott Huntsman, Melissa Garcia, Donglei Hu, Rongling Li, Brock A Beamer, Kushang V Patel, Ermeg L Akylbekova, Joe C Files, Cheryl L Hardy, Sarah G Buxbaum, Herman A Taylor, David Reich, Tamara B Harris, Elad Ziv
Affiliations

Admixture mapping of white cell count: genetic locus responsible for lower white blood cell count in the Health ABC and Jackson Heart studies

Michael A Nalls et al. Am J Hum Genet. 2008 Jan.

Erratum in

  • Am J Hum Genet. 2008 Feb;82(2):532

Abstract

White blood cell count (WBC) is an important clinical marker that varies among different ethnic groups. African Americans are known to have a lower WBC than European Americans. We surveyed the entire genome for loci underlying this difference in WBC by using admixture mapping. We analyzed data from African American participants in the Health, Aging, and Body Composition Study and the Jackson Heart Study. Participants of both studies were genotyped across >or= 1322 single nucleotide polymorphisms that were pre-selected to be informative for African versus European ancestry and span the entire genome. We used these markers to estimate genetic ancestry in each chromosomal region and then tested the association between WBC and genetic ancestry at each locus. We found a locus on chromosome 1q strongly associated with WBC (p < 10(-12)). The strongest association was with a marker known to affect the expression of the Duffy blood group antigen. Participants who had both copies of the common West African allele had a mean WBC of 4.9 (SD 1.3); participants who had both common European alleles had a mean WBC of 7.1 (SD 1.3). This variant explained approximately 20% of population variation in WBC. We used admixture mapping, a novel method for conducting genetic-association studies, to find a region that was significantly associated with WBC on chromosome 1q. Additional studies are needed to determine the biological mechanism for this effect and its clinical implications.

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Figures

Figure 1
Figure 1
Association of White Blood Cell Count with Increasing Percent European Ancestry from STRUCTURE Estimates in the Health ABC Population Results from nonparametric lowess smoothing analysis, trend significance p = 3.3 × 10−9.
Figure 2
Figure 2
LOD Scores of Case-Control Analysis Results from ANCESTRYMAP for initial genome-wide scan in Health ABC, as well as replication in the Jackson Heart Study cohort. Broken line signifies significance threshold.
Figure 3
Figure 3
Posterior Probability Distribution for the Position of the Disease Locus, Based on ANCESTRYMAP Scans in the Health ABC Study, Represented by the Black Line, and Jackson Heart Study, Represented by the Gray Line The 99% confidence interval for the position of the disease locus in the Jackson Heart Study is 155.46-156.36 Mb and is centered on rs2814778.
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