TY - JOUR
T1 - Genetic loci implicated in erythroid differentiation and cell cycle regulation are associated with red blood cell traits
AU - Ding, Keyue
AU - Shameer, Khader
AU - Jouni, Hayan
AU - Masys, Daniel R.
AU - Jarvik, Gail P.
AU - Kho, Abel N.
AU - Ritchie, Marylyn D.
AU - McCarty, Catherine A.
AU - Chute, Christopher G.
AU - Manolio, Teri A.
AU - Kullo, Iftikhar J.
N1 - Funding Information:
Grant Support: The eMERGE network was initiated and funded by the National Human Genome Research Institute, with additional funding from National Institute of General Medical Sciences through the following grants: U01-HG-04599 (Mayo Clinic), U01-HG-004610 (GHC), U01-HG-004608 (MC), U01HG004609 (NU), and U01-HG-04603 (VUMC, also serving as the administrative coordinating center).
PY - 2012/5
Y1 - 2012/5
N2 - 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.
AB - 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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U2 - 10.1016/j.mayocp.2012.01.016
DO - 10.1016/j.mayocp.2012.01.016
M3 - Article
C2 - 22560525
AN - SCOPUS:84860699846
SN - 0025-6196
VL - 87
SP - 461
EP - 474
JO - Mayo Clinic proceedings
JF - Mayo Clinic proceedings
IS - 5
ER -