Admixture mapping and investigation of genetic associations of white blood cell count

Abstract

This study analyzes variation in WBC among participants in the Health, Aging and Body Composition study (Health ABC). First, white blood cell (WBC) counts are compared among African Americans and European Americans in the study, confirming a significant difference. These population-based differences in WBC are also described in literature as differing significantly between different African populations, Caribbean populations, Central and South American groups, Asian populations and Europeans (Bain et al., 1984; Saxena and Wong, 1990; Bain, 1996; Menard et al., 2003; Hsieh et al., 2007). Ancestry informative markers are used to estimate the individual ancestry of the African Americans in the study. There is a significant association of low WBC with a higher proportion of African ancestry. An admixture mapping approach is used to identify a novel locus [independently identified in a separate admixture scan in the Jackson Heart Study (JHS)] that influences WBC levels. The peaks of association in both studies localize to a region ~0.9 Mb centered on the Duffy Antigen Receptor for Chemokines gene (DARC [MIM 110700]). Second, the functionality at the DARC locus is determined by investigating associations between DARC and neutrophils, lymnphocytes, monocytes, basophils and eosinophils. This investigation shows a consistent genetic effect at this locus associated with all of these differential cell types. Third, the association of DARC with all marrow derived cell lineages and red blood cell levels is evaluated. It is shown that, in addition to known associations between the DARC gene and malarial resistance (Miller et al., 1976; Livingstone, 1984) often associated with red blood cells, the DARC gene is also associated with WBC levels (Nalls et al., 2008). Selective pressure at this genetic locus may be related to its effect on WBC that may have contributed to the fixation of the FY- allele in some populations.