title: Genetic Loci implicated in erythroid differentiation and cell cycle regulation are associated with red blood cell traits.
abstract: OBJECTIVE
  To identify common genetic variants influencing red blood cell (RBC) traits.
  
  
  METHODS
  We performed a genomewide association study from June 2008 through July 2011 of hemoglobin, hematocrit, RBC count, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration in 12,486 patients of European ancestry from the electronic MEdical Records and Genomics (eMERGE) network. We developed an electronic medical record-based algorithm that included individuals who had RBC measurements obtained for clinical care and excluded values measured in the setting of hematopoietic disorders, comorbid conditions, or medications known to affect RBC production or a recent history of blood loss.
  
  
  RESULTS
  We identified 4 new genetic loci and replicated 11 loci previously reported to be associated with one or more RBC traits in individuals of European ancestry. Notably, genes present in 3 of the 4 newly identified loci (THRB, PTPLAD1, CDT1) and in 6 of the 11 replicated loci (KLF1, ALDH8A1, CCND3, SPTA1, FBXO7, TFR2/EPO) are implicated in erythroid differentiation and regulation of cell cycle in hematopoietic stem cells.
  
  
  CONCLUSIONS
  Genes in the erythroid differentiation and cell cycle regulation pathways influence interindividual variation in RBC indices. Our results provide insights into the molecular basis underlying variation in RBC traits.
authors.affiliation: Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Keyue
authors.initials: K
authors.lastname: Ding
authors.forename: Khader
authors.initials: K
authors.lastname: Shameer
authors.forename: Hayan
authors.initials: H
authors.lastname: Jouni
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Masys
authors.forename: Gail P
authors.initials: GP
authors.lastname: Jarvik
authors.forename: Abel N
authors.initials: AN
authors.lastname: Kho
authors.forename: Marylyn D
authors.initials: MD
authors.lastname: Ritchie
authors.forename: Catherine A
authors.initials: CA
authors.lastname: McCarty
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Chute
authors.forename: Teri A
authors.initials: TA
authors.lastname: Manolio
authors.forename: Iftikhar J
authors.initials: IJ
authors.lastname: Kullo
mesh_terms: D002454:Cell Differentiation / Q000235:genetics; D004909:Erythrocyte Indices / Q000235:genetics*; D005787:Gene Frequency; D056726:Genetic Association Studies; D005828:Genetics, Population; D006454:Hemoglobins / Q000235:genetics*; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci / Q000235:genetics*; D044465:White People / Q000235:genetics*
chemical_list: D006454:Hemoglobins