GWAS of blood cell traits identifies novel associated loci and epistatic interactions in caucasian and African-American children

Jin Li, Joseph T. Glessner, Haitao Zhang, Cuiping Hou, Zhi Wei, Jonathan P. Bradfield, Frank D. Mentch, Yiran Guo, Cecilia Kim, Qianghua Xia, Rosetta M. Chiavacci, Kelly A. Thomas, Haijun Qiu, Struan F.A. Grant, Susan L. Furth, Hakon Hakonarson, Patrick M.A. Sleiman

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

Hematological traits are important clinical indicators, the genetic determinants of which have not been fully investigated. Common measures of hematological traits include red blood cell (RBC) count, hemoglobin concentration (HGB), hematocrit (HCT), mean corpuscular hemoglobin (MCH), MCH concentration (MCHC), mean corpuscular volume (MCV), platelet count (PLT) and white blood cell (WBC) count. We carried out a genome-wide association study of the eight common hematological traits among 7943 African-American children and 6234 Caucasian children. In African Americans, we report five novel associations of HBE1 variants with HCT and MCHC, the alpha-globin gene cluster variants with RBC and MCHC, and a variant at the ARHGEF3 locus with PLT, as well as replication of four previously reported loci at genome-wide significance. In Caucasians, we report a novel association of variants at the COPZ1 locus with PLT as well as replication of four previously reported loci at genome-wide significance. Extended analysis of an association observed between MCH and the alpha-globin gene cluster variants demonstrated independent effects and epistatic interaction at the locus, impacting the risk of iron deficiency anemia in African Americans with specific genotype states. In summary, we extend the understanding of genetic variants underlying hematological traits based on analyses in African-American children.

Original languageEnglish (US)
Article numberdds534
Pages (from-to)1457-1464
Number of pages8
JournalHuman Molecular Genetics
Volume22
Issue number7
DOIs
StatePublished - Apr 2013

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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