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PMID: 23446634 Published · ppublish English Journal Article Research Support, American Recovery and Reinvestment Act Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't

Genome-wide association analysis of red blood cell traits in African Americans: the COGENT Network.

Human molecular genetics ·Vol. 22 ·No. 12 ·2013-06-15 ·Pages 2529-38

Chen Z, Tang H, Qayyum R, Schick UM, Nalls MA, Handsaker R, Li J, Lu Y, Yanek LR, Keating B, Meng Y, van Rooij FJ, 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, BioBank Japan Project, CHARGE Consortium, Thomson C, Ziv E, Singleton AB, Loos RJ, Sleiman PM, Ganesh S, McCarroll S, Becker DM, Wilson JG, Lettre G, Reiner AP

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.

MeSH Terms
Adolescent Adult African Americans/genetics Child Chromosomes, Human, Pair 16/genetics Cohort Studies Erythrocyte Count Erythrocyte Indices Erythrocytes/cytology,metabolism Female Genome-Wide Association Study Hemoglobins/genetics Humans Male Polymorphism, Single Nucleotide Whites/genetics Young Adult alpha-Globins/genetics
Chemicals
Hemoglobins alpha-Globins
Authors & Affiliations
38 authors, click to expand affiliations / ORCID
Chen Zhao
Division of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ 85724, USA.
Tang Hua
Qayyum Rehan
Schick Ursula M
Nalls Michael A
Handsaker Robert
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
BioBank Japan Project
CHARGE Consortium
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
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Article Info
Journal
Human molecular genetics
Abbr.
Hum Mol Genet
ISSN
1460-2083
DOI
10.1093/hmg/ddt087
Published
2013-06-15
Epub
2013-00-26
Pages
2529-38
Language
English
Region
England
NLM ID
9208958
PMCID
PMC3658166
Subset
IM
Grants
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PubMed source DOI: 10.1093/hmg/ddt087 PMC Full Text View journal details
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