Abstract
Red blood cell, white blood cell, and platelet measures, including their count, sub-type and volume, are important diagnostic and prognostic clinical parameters for several human diseases. To identify novel loci associated with hematological traits, and compare the architecture of these phenotypes between ethnic groups, the CARe Project genotyped 49,094 single nucleotide polymorphisms (SNPs) that capture variation in ~2,100 candidate genes in DNA of 23,439 Caucasians and 7,112 African Americans from five population-based cohorts. We found strong novel associations between erythrocyte phenotypes and the glucose-6 phosphate dehydrogenase (G6PD) A-allele in African Americans (rs1050828, P < 2.0 × 10−13, T-allele associated with lower red blood cell count, hemoglobin, and hematocrit, and higher mean corpuscular volume), and between platelet count and a SNP at the tropomyosin-4 (TPM4) locus (rs8109288, P = 3.0 × 10−7 in Caucasians; P = 3.0 × 10−7 in African Americans, T-allele associated with lower platelet count). We strongly replicated many genetic associations to blood cell phenotypes previously established in Caucasians. A common variant of the α-globin (HBA2-HBA1) locus was associated with red blood cell traits in African Americans, but not in Caucasians (rs1211375, P < 7 × 10−8, A-allele associated with lower hemoglobin, mean corpuscular hemoglobin, and mean corpuscular volume). Our results show similarities but also differences in the genetic regulation of hematological traits in European- and African-derived populations, and highlight the role of natural selection in shaping these differences.
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Acknowledgments
The authors wish to acknowledge the support of the National Heart, Lung, and Blood Institute and the contributions of the research institutions, study investigators, field staff and study participants in creating this resource for biomedical research. The grants and contracts that have supported CARe are listed at http://public.nhlbi.nih.gov/GeneticsGenomics/home/care.aspx. Additional support for this work was provided by the Fondation de l’Institut de Cardiologie de Montréal (to G.L.), and by NIH R01 HL71862-06 and ARRA N000949304 (to A.P.R.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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A. P. Reiner and G. Lettre co-directed the study.
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Lo, K.S., Wilson, J.G., Lange, L.A. et al. Genetic association analysis highlights new loci that modulate hematological trait variation in Caucasians and African Americans. Hum Genet 129, 307–317 (2011). https://doi.org/10.1007/s00439-010-0925-1
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DOI: https://doi.org/10.1007/s00439-010-0925-1