Genome-wide association analysis of red blood cell traits in African Americans: The cogent network

Zhao Chen, Hua Tang, Rehan Qayyum, Ursula M. Schick, Michael A. Nalls, Rober Handsaker, Jin Li, Yingchang Lu, Lisa R. Yanek, Brendan Keating, Yan Meng, Frank J.A. Van Rooij, Yukinori Okada, Michiaki Kubo, Laura Rasmussen-Torvik, Margaux F. Keller, Leslie Lange, Michele Evans, Erwin P. Bottinger, Michael D. LindermanDouglas M. Ruderfer, Hakon Hakonarson, George Papanicolaou, Alan B. Zonderman, Omri Gottesman, Cynthia Thomson, Elad Ziv, Andrew B. Singleton, Ruth J.F. Loos, Patrick M.A. Sleiman, Santhi Ganesh, Steven McCarroll, Diane M. Becker, James G. Wilson, Guillaume Lettre, Alexander P. Reiner

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Laboratory red blood cell (RBC) measurements are clinically important, heritable and differ among ethnic groups. To identify genetic variants that contribute to RBC phenotypes in African Americans (AAs), we conducted a genome-wide association study in up to ~16 500 AAs. The alpha-globin locus on chromosome 16pter [lead SNP rs13335629 in ITFG3 gene; P < 1E-13 for hemoglobin (Hgb), RBC count, mean corpuscular volume (MCV), MCH and MCHC] and the G6PD locus on Xq28 [lead SNP rs1050828; P < 1E - 13 for Hgb, hematocrit (Hct), MCV, RBC count and red cell distribution width (RDW)] were each associated with multiple RBC traits. At the alpha-globin region, both the common African 3.7 kb deletion and common single nucleotide polymorphisms (SNPs) appear to contribute independently to RBC phenotypes among AAs. In the 2p21 region, we identified a novel variant of PRKCE distinctly associated with Hct in AAs. In a genome-wide admixture mapping scan, local European ancestry at the 6p22 region containing HFE and LRRC16A was associated with higher Hgb. LRRC16A has been previously associated with the platelet count and mean platelet volume in AAs, but not with Hgb. Finally, we extended to AAs the findings of association of erythrocyte traits with several loci previously reported in Europeans and/or Asians, including CD164 and HBS1L-MYB. In summary, this large-scale genome-wide analysis in AAs has extended the importance of several RBC-associated genetic loci to AAs and identified allelic heterogeneity and pleiotropy at several previously known genetic loci associated with blood cell traits in AAs.

Original languageEnglish
Pages (from-to)2529-2538
Number of pages10
JournalHuman molecular genetics
Volume22
Issue number12
DOIs
Publication statusPublished - 01-06-2013

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Genome-Wide Association Study
African Americans
Erythrocytes
Erythrocyte Indices
Hemoglobins
Single Nucleotide Polymorphism
alpha-Globins
Erythrocyte Count
Genetic Loci
Hematocrit
Genome
Mean Platelet Volume
Phenotype
Platelet Count
Ethnic Groups
Blood Cells
Chromosomes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Chen, Z., Tang, H., Qayyum, R., Schick, U. M., Nalls, M. A., Handsaker, R., ... Reiner, A. P. (2013). Genome-wide association analysis of red blood cell traits in African Americans: The cogent network. Human molecular genetics, 22(12), 2529-2538. https://doi.org/10.1093/hmg/ddt087
Chen, Zhao ; Tang, Hua ; Qayyum, Rehan ; Schick, Ursula M. ; Nalls, Michael A. ; Handsaker, Rober ; Li, Jin ; Lu, Yingchang ; Yanek, Lisa R. ; Keating, Brendan ; Meng, Yan ; Van Rooij, Frank J.A. ; Okada, Yukinori ; Kubo, Michiaki ; Rasmussen-Torvik, Laura ; Keller, Margaux F. ; Lange, Leslie ; Evans, Michele ; Bottinger, Erwin P. ; Linderman, Michael D. ; Ruderfer, Douglas M. ; Hakonarson, Hakon ; Papanicolaou, George ; Zonderman, Alan B. ; Gottesman, Omri ; Thomson, Cynthia ; Ziv, Elad ; Singleton, Andrew B. ; Loos, Ruth J.F. ; Sleiman, Patrick M.A. ; Ganesh, Santhi ; McCarroll, Steven ; Becker, Diane M. ; Wilson, James G. ; Lettre, Guillaume ; Reiner, Alexander P. / Genome-wide association analysis of red blood cell traits in African Americans : The cogent network. In: Human molecular genetics. 2013 ; Vol. 22, No. 12. pp. 2529-2538.
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abstract = "Laboratory red blood cell (RBC) measurements are clinically important, heritable and differ among ethnic groups. To identify genetic variants that contribute to RBC phenotypes in African Americans (AAs), we conducted a genome-wide association study in up to ~16 500 AAs. The alpha-globin locus on chromosome 16pter [lead SNP rs13335629 in ITFG3 gene; P < 1E-13 for hemoglobin (Hgb), RBC count, mean corpuscular volume (MCV), MCH and MCHC] and the G6PD locus on Xq28 [lead SNP rs1050828; P < 1E - 13 for Hgb, hematocrit (Hct), MCV, RBC count and red cell distribution width (RDW)] were each associated with multiple RBC traits. At the alpha-globin region, both the common African 3.7 kb deletion and common single nucleotide polymorphisms (SNPs) appear to contribute independently to RBC phenotypes among AAs. In the 2p21 region, we identified a novel variant of PRKCE distinctly associated with Hct in AAs. In a genome-wide admixture mapping scan, local European ancestry at the 6p22 region containing HFE and LRRC16A was associated with higher Hgb. LRRC16A has been previously associated with the platelet count and mean platelet volume in AAs, but not with Hgb. Finally, we extended to AAs the findings of association of erythrocyte traits with several loci previously reported in Europeans and/or Asians, including CD164 and HBS1L-MYB. In summary, this large-scale genome-wide analysis in AAs has extended the importance of several RBC-associated genetic loci to AAs and identified allelic heterogeneity and pleiotropy at several previously known genetic loci associated with blood cell traits in AAs.",
author = "Zhao Chen and Hua Tang and Rehan Qayyum and Schick, {Ursula M.} and Nalls, {Michael A.} and Rober Handsaker and Jin Li and Yingchang Lu and Yanek, {Lisa R.} and Brendan Keating and Yan Meng and {Van Rooij}, {Frank J.A.} and Yukinori Okada and Michiaki Kubo and Laura Rasmussen-Torvik and Keller, {Margaux F.} and Leslie Lange and Michele Evans and Bottinger, {Erwin P.} and Linderman, {Michael D.} and Ruderfer, {Douglas M.} and Hakon Hakonarson and George Papanicolaou and Zonderman, {Alan B.} and Omri Gottesman and Cynthia Thomson and Elad Ziv and Singleton, {Andrew B.} and Loos, {Ruth J.F.} and Sleiman, {Patrick M.A.} and Santhi Ganesh and Steven McCarroll and Becker, {Diane M.} and Wilson, {James G.} and Guillaume Lettre and Reiner, {Alexander P.}",
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Chen, Z, Tang, H, Qayyum, R, Schick, UM, Nalls, MA, Handsaker, R, Li, J, Lu, Y, Yanek, LR, Keating, B, Meng, Y, Van Rooij, FJA, Okada, Y, Kubo, M, Rasmussen-Torvik, L, Keller, MF, Lange, L, Evans, M, Bottinger, EP, Linderman, MD, Ruderfer, DM, Hakonarson, H, Papanicolaou, G, Zonderman, AB, Gottesman, O, Thomson, C, Ziv, E, Singleton, AB, Loos, RJF, Sleiman, PMA, Ganesh, S, McCarroll, S, Becker, DM, Wilson, JG, Lettre, G & Reiner, AP 2013, 'Genome-wide association analysis of red blood cell traits in African Americans: The cogent network', Human molecular genetics, vol. 22, no. 12, pp. 2529-2538. https://doi.org/10.1093/hmg/ddt087

Genome-wide association analysis of red blood cell traits in African Americans : The cogent network. / Chen, Zhao; Tang, Hua; Qayyum, Rehan; Schick, Ursula M.; Nalls, Michael A.; Handsaker, Rober; Li, Jin; Lu, Yingchang; Yanek, Lisa R.; Keating, Brendan; Meng, Yan; Van Rooij, Frank J.A.; Okada, Yukinori; Kubo, Michiaki; Rasmussen-Torvik, Laura; Keller, Margaux F.; Lange, Leslie; Evans, Michele; Bottinger, Erwin P.; Linderman, Michael D.; Ruderfer, Douglas M.; Hakonarson, Hakon; Papanicolaou, George; Zonderman, Alan B.; Gottesman, Omri; Thomson, Cynthia; Ziv, Elad; Singleton, Andrew B.; Loos, Ruth J.F.; Sleiman, Patrick M.A.; Ganesh, Santhi; McCarroll, Steven; Becker, Diane M.; Wilson, James G.; Lettre, Guillaume; Reiner, Alexander P.

In: Human molecular genetics, Vol. 22, No. 12, 01.06.2013, p. 2529-2538.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genome-wide association analysis of red blood cell traits in African Americans

T2 - The cogent network

AU - Chen, Zhao

AU - Tang, Hua

AU - Qayyum, Rehan

AU - Schick, Ursula M.

AU - Nalls, Michael A.

AU - Handsaker, Rober

AU - Li, Jin

AU - Lu, Yingchang

AU - Yanek, Lisa R.

AU - Keating, Brendan

AU - Meng, Yan

AU - Van Rooij, Frank J.A.

AU - Okada, Yukinori

AU - Kubo, Michiaki

AU - Rasmussen-Torvik, Laura

AU - Keller, Margaux F.

AU - Lange, Leslie

AU - Evans, Michele

AU - Bottinger, Erwin P.

AU - Linderman, Michael D.

AU - Ruderfer, Douglas M.

AU - Hakonarson, Hakon

AU - Papanicolaou, George

AU - Zonderman, Alan B.

AU - Gottesman, Omri

AU - Thomson, Cynthia

AU - Ziv, Elad

AU - Singleton, Andrew B.

AU - Loos, Ruth J.F.

AU - Sleiman, Patrick M.A.

AU - Ganesh, Santhi

AU - McCarroll, Steven

AU - Becker, Diane M.

AU - Wilson, James G.

AU - Lettre, Guillaume

AU - Reiner, Alexander P.

PY - 2013/6/1

Y1 - 2013/6/1

N2 - Laboratory red blood cell (RBC) measurements are clinically important, heritable and differ among ethnic groups. To identify genetic variants that contribute to RBC phenotypes in African Americans (AAs), we conducted a genome-wide association study in up to ~16 500 AAs. The alpha-globin locus on chromosome 16pter [lead SNP rs13335629 in ITFG3 gene; P < 1E-13 for hemoglobin (Hgb), RBC count, mean corpuscular volume (MCV), MCH and MCHC] and the G6PD locus on Xq28 [lead SNP rs1050828; P < 1E - 13 for Hgb, hematocrit (Hct), MCV, RBC count and red cell distribution width (RDW)] were each associated with multiple RBC traits. At the alpha-globin region, both the common African 3.7 kb deletion and common single nucleotide polymorphisms (SNPs) appear to contribute independently to RBC phenotypes among AAs. In the 2p21 region, we identified a novel variant of PRKCE distinctly associated with Hct in AAs. In a genome-wide admixture mapping scan, local European ancestry at the 6p22 region containing HFE and LRRC16A was associated with higher Hgb. LRRC16A has been previously associated with the platelet count and mean platelet volume in AAs, but not with Hgb. Finally, we extended to AAs the findings of association of erythrocyte traits with several loci previously reported in Europeans and/or Asians, including CD164 and HBS1L-MYB. In summary, this large-scale genome-wide analysis in AAs has extended the importance of several RBC-associated genetic loci to AAs and identified allelic heterogeneity and pleiotropy at several previously known genetic loci associated with blood cell traits in AAs.

AB - Laboratory red blood cell (RBC) measurements are clinically important, heritable and differ among ethnic groups. To identify genetic variants that contribute to RBC phenotypes in African Americans (AAs), we conducted a genome-wide association study in up to ~16 500 AAs. The alpha-globin locus on chromosome 16pter [lead SNP rs13335629 in ITFG3 gene; P < 1E-13 for hemoglobin (Hgb), RBC count, mean corpuscular volume (MCV), MCH and MCHC] and the G6PD locus on Xq28 [lead SNP rs1050828; P < 1E - 13 for Hgb, hematocrit (Hct), MCV, RBC count and red cell distribution width (RDW)] were each associated with multiple RBC traits. At the alpha-globin region, both the common African 3.7 kb deletion and common single nucleotide polymorphisms (SNPs) appear to contribute independently to RBC phenotypes among AAs. In the 2p21 region, we identified a novel variant of PRKCE distinctly associated with Hct in AAs. In a genome-wide admixture mapping scan, local European ancestry at the 6p22 region containing HFE and LRRC16A was associated with higher Hgb. LRRC16A has been previously associated with the platelet count and mean platelet volume in AAs, but not with Hgb. Finally, we extended to AAs the findings of association of erythrocyte traits with several loci previously reported in Europeans and/or Asians, including CD164 and HBS1L-MYB. In summary, this large-scale genome-wide analysis in AAs has extended the importance of several RBC-associated genetic loci to AAs and identified allelic heterogeneity and pleiotropy at several previously known genetic loci associated with blood cell traits in AAs.

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