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PMID: 19862010 Published · ppublish English Journal Article

Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium.

Nature genetics ·Vol. 41 ·No. 11 ·2009-11-00 ·Pages 1191-8

Ganesh SK, Zakai NA, van Rooij FJ, Soranzo N, Smith AV, Nalls MA, Chen MH, Kottgen A, Glazer NL, Dehghan A, Kuhnel B, Aspelund T, Yang Q, Tanaka T, Jaffe A, Bis JC, Verwoert GC, Teumer A, Fox CS, Guralnik JM, Ehret GB, Rice K, Felix JF, Rendon A, Eiriksdottir G, Levy D, Patel KV, Boerwinkle E, Rotter JI, Hofman A, Sambrook JG, Hernandez DG, Zheng G, Bandinelli S, Singleton AB, Coresh J, Lumley T, Uitterlinden AG, Vangils JM, Launer LJ, Cupples LA, Oostra BA, Zwaginga JJ, Ouwehand WH, Thein SL, Meisinger C, Deloukas P, Nauck M, Spector TD, Gieger C, Gudnason V, van Duijn CM, Psaty BM, Ferrucci L, Chakravarti A, Greinacher A, O'Donnell CJ, Witteman JC, Furth S, Cushman M, Harris TB, Lin JP

Abstract

Measurements of erythrocytes within the blood are important clinical traits and can indicate various hematological disorders. We report here genome-wide association studies (GWAS) for six erythrocyte traits, including hemoglobin concentration (Hb), hematocrit (Hct), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) and red blood cell count (RBC). We performed an initial GWAS in cohorts of the CHARGE Consortium totaling 24,167 individuals of European ancestry and replication in additional independent cohorts of the HaemGen Consortium totaling 9,456 individuals. We identified 23 loci significantly associated with these traits in a meta-analysis of the discovery and replication cohorts (combined P values ranging from 5 x 10(-8) to 7 x 10(-86)). Our findings include loci previously associated with these traits (HBS1L-MYB, HFE, TMPRSS6, TFR2, SPTA1) as well as new associations (EPO, TFRC, SH2B3 and 15 other loci). This study has identified new determinants of erythrocyte traits, offering insight into common variants underlying variation in erythrocyte measures.

MeSH Terms
Blood Pressure/genetics Cell Line Cohort Studies Endothelial Cells/metabolism Erythrocytes/metabolism Gene Expression Genome, Human Genome-Wide Association Study Humans Hypertension/genetics Phenotype Polymorphism, Single Nucleotide Quantitative Trait Loci
Authors & Affiliations
62 authors, click to expand affiliations / ORCID
Ganesh Santhi K
National Human Genome Research Institute, Division of Intramural Research, Bethesda, MD, USA. [email protected]
Zakai Neil A
van Rooij Frank J A
Soranzo Nicole
Smith Albert V
Nalls Michael A
Chen Ming-Huei
Kottgen Anna
Glazer Nicole L
Dehghan Abbas
Kuhnel Brigitte
Aspelund Thor
Yang Qiong
Tanaka Toshiko
Jaffe Andrew
Bis Joshua C M
Verwoert Germaine C
Teumer Alexander
Fox Caroline S
Guralnik Jack M
Ehret Georg B
Rice Kenneth
Felix Janine F
Rendon Augusto
Eiriksdottir Gudny
Levy Daniel
Patel Kushang V
Boerwinkle Eric
Rotter Jerome I
Hofman Albert
Sambrook Jennifer G
Hernandez Dena G
Zheng Gang
Bandinelli Stefania
Singleton Andrew B
Coresh Josef
Lumley Thomas
Uitterlinden André G
Vangils Janine M
Launer Lenore J
Cupples L Adrienne
Oostra Ben A
Zwaginga Jaap-Jan
Ouwehand Willem H
Thein Swee-Lay
Meisinger Christa
Deloukas Panos
Nauck Matthias
Spector Tim D
Gieger Christian
Gudnason Vilmundur
van Duijn Cornelia M
Psaty Bruce M
Ferrucci Luigi
Chakravarti Aravinda
Greinacher Andreas
O'Donnell Christopher J
Witteman Jacqueline C M
Furth Susan
Cushman Mary
Harris Tamara B
Lin Jing-Ping
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Article Info
Journal
Nature genetics
Abbr.
Nat Genet
ISSN
1546-1718
DOI
10.1038/ng.466
Email
[email protected]
Published
2009-11-00
Epub
2009-00-11
Pages
1191-8
Language
English
Region
United States
NLM ID
9216904
PMCID
PMC2778265
Subset
IM
Grants
NIDDK NIH HHS · P30 DK063491-05 · United States
NIDDK NIH HHS · U01 DK066174 · United States
NHLBI NIH HHS · R01 HL086694 · United States
Medical Research Council · G0000111 · United Kingdom
NHLBI NIH HHS · R01 HL086694-01A1 · United States
NIDDK NIH HHS · P30 DK063491-039004 · United States
NHLBI NIH HHS · R01 HL086694-03 · United States
NIDDK NIH HHS · P30 DK063491-029004 · United States
NIDDK NIH HHS · P30 DK063491-019004 · United States
NIDDK NIH HHS · P30 DK063491-049004 · United States
NIDDK NIH HHS · K24 DK078737 · United States
NIDDK NIH HHS · P30 DK063491 · United States
NHLBI NIH HHS · R01 HL086694-02 · United States
Corrections
CommentIn
PMID: 19862006
External Links
PubMed source DOI: 10.1038/ng.466 PMC Full Text View journal details
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