Genetic loci implicated in erythroid differentiation and cell cycle regulation are associated with red blood cell traits

Keyue Ding, Khader Shameer, Hayan Jouni, Daniel R. Masys, Gail P. Jarvik, Abel N. Kho, Marylyn D. Ritchie, Catherine A. McCarty, Christopher G. Chute, Teri A. Manolio, Iftikhar Jan Kullo

Research output: Contribution to journalArticle

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Abstract

Objective: To identify common genetic variants influencing red blood cell (RBC) traits. Patients and 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)461-474
Number of pages14
JournalMayo Clinic Proceedings
Volume87
Issue number5
DOIs
StatePublished - 2012

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Erythroid Cells
Genetic Loci
Cell Cycle
Erythrocyte Indices
Erythrocytes
Electronic Health Records
Erythrocyte Count
Hematopoietic Stem Cells
Genomics
Hematocrit
Genes
Hemoglobins

ASJC Scopus subject areas

  • Medicine(all)

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Genetic loci implicated in erythroid differentiation and cell cycle regulation are associated with red blood cell traits. / Ding, Keyue; Shameer, Khader; Jouni, Hayan; Masys, Daniel R.; Jarvik, Gail P.; Kho, Abel N.; Ritchie, Marylyn D.; McCarty, Catherine A.; Chute, Christopher G.; Manolio, Teri A.; Kullo, Iftikhar Jan.

In: Mayo Clinic Proceedings, Vol. 87, No. 5, 2012, p. 461-474.

Research output: Contribution to journalArticle

Ding, K, Shameer, K, Jouni, H, Masys, DR, Jarvik, GP, Kho, AN, Ritchie, MD, McCarty, CA, Chute, CG, Manolio, TA & Kullo, IJ 2012, 'Genetic loci implicated in erythroid differentiation and cell cycle regulation are associated with red blood cell traits', Mayo Clinic Proceedings, vol. 87, no. 5, pp. 461-474. https://doi.org/10.1016/j.mayocp.2012.01.016
Ding, Keyue ; Shameer, Khader ; Jouni, Hayan ; Masys, Daniel R. ; Jarvik, Gail P. ; Kho, Abel N. ; Ritchie, Marylyn D. ; McCarty, Catherine A. ; Chute, Christopher G. ; Manolio, Teri A. ; Kullo, Iftikhar Jan. / Genetic loci implicated in erythroid differentiation and cell cycle regulation are associated with red blood cell traits. In: Mayo Clinic Proceedings. 2012 ; Vol. 87, No. 5. pp. 461-474.
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abstract = "Objective: To identify common genetic variants influencing red blood cell (RBC) traits. Patients and 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. Conclusion: 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.",
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