Genetic association analysis highlights new loci that modulate hematological trait variation in Caucasians and African Americans

Hum Genet. 2011 Mar;129(3):307-17. doi: 10.1007/s00439-010-0925-1. Epub 2010 Dec 12.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alpha-Globulins / genetics
  • Black or African American / genetics*
  • Blood Cell Count*
  • Cohort Studies
  • Erythrocyte Count
  • Erythrocyte Indices / genetics
  • Erythrocytes / cytology
  • Erythrocytes / enzymology
  • Female
  • Genetic Association Studies*
  • Genetic Loci*
  • Glucosephosphate Dehydrogenase / genetics
  • Hemoglobins / genetics
  • Humans
  • Male
  • Middle Aged
  • Platelet Count
  • Polymorphism, Single Nucleotide / genetics
  • Quantitative Trait, Heritable*
  • White People / genetics*


  • Alpha-Globulins
  • Hemoglobins
  • Glucosephosphate Dehydrogenase
  • glucose-6-phosphate dehydrogenase A-