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 J. Kullo

doi:10.1016/j.mayocp.2012.01.016

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 J. Kullo

Research output: Contribution to journal › Article › peer-review

32 Scopus citations

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 language	English (US)
Pages (from-to)	461-474
Number of pages	14
Journal	Mayo Clinic Proceedings
Volume	87
Issue number	5
DOIs	https://doi.org/10.1016/j.mayocp.2012.01.016
State	Published - May 2012

Bibliographical note

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).

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Copyright 2017 Elsevier B.V., All rights reserved.

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@article{ac75fe733b414fb2a8e619a86aeaf608,

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. 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.",

author = "Keyue Ding and Khader Shameer and Hayan Jouni and Masys, {Daniel R.} and Jarvik, {Gail P.} and Kho, {Abel N.} and Ritchie, {Marylyn D.} and McCarty, {Catherine A.} and Chute, {Christopher G.} and Manolio, {Teri A.} and Kullo, {Iftikhar J.}",

note = "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). Copyright: Copyright 2017 Elsevier B.V., All rights reserved.",

year = "2012",

month = may,

doi = "10.1016/j.mayocp.2012.01.016",

language = "English (US)",

volume = "87",

pages = "461--474",

journal = "Mayo Clinic Proceedings",

issn = "0025-6196",

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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). Copyright: Copyright 2017 Elsevier B.V., All rights reserved.

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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JO - Mayo Clinic Proceedings

JF - Mayo Clinic Proceedings

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ER -

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

Abstract

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