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Admixture mapping of white cell count: genetic locus responsible for lower white blood cell count in the Health ABC and Jackson Heart studies |
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| Authors: | Nalls Michael A Wilson James G Patterson Nick J Tandon Arti Zmuda Joseph M Huntsman Scott Garcia Melissa Hu Donglei Li Rongling Beamer Brock A Patel Kushang V Akylbekova Ermeg L Files Joe C Hardy Cheryl L Buxbaum Sarah G Taylor Herman A Reich David Harris Tamara B Ziv Elad |
| Affiliation: | 1 Laboratory of Epidemiology, Demography and Biometry, Intramural Research Program, National Institute on Aging, Bethesda, MD 20892, USA 2 V.A. Medical Center and the University of Mississippi Medical Center, Jackson, MS 39216, USA 3 Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA 4 Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA 5 Institute for Human Genetics, Division of General Internal Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA 6 Department of Preventive Medicine, Division of Biostatistics and Epidemiology, University of Tennessee, Memphis, Memphis, TN 38163, USA 7 Division of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA 8 Jackson Heart Study Coordinating Center, Jackson State University, Jackson, MS 39213, USA 9 Department of Medicine, Division of Hematology, University of Mississippi Medical Center, Jackson, MS 39216, USA 10 Jackson State University, Tougaloo College, and the University of Mississippi Medical Center, Jackson, MS 39216, USA 11 Department of Genetics, Harvard Medical School, Boston, MA 02115, USA |
| 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 ≥ 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 ~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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