Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium

被引：288

作者：

Ganesh, Santhi K. ^{[1
,2
,3
]}

Zakai, Neil A. ^{[4
,5
]}

van Rooij, Frank J. A. ^{[6
,7
]}

Soranzo, Nicole ^{[8
,9
]}

Smith, Albert V. ^{[10
]}

Nalls, Michael A.

Chen, Ming-Huei ^{[12
,13
]}

Kottgen, Anna ^{[14
]}

Glazer, Nicole L. ^{[15
,16
]}

Dehghan, Abbas ^{[6
,7
]}

Kuhnel, Brigitte ^{[17
]}

Aspelund, Thor ^{[10
,18
]}

Yang, Qiong ^{[12
,19
]}

Tanaka, Toshiko ^{[20
,21
]}

Jaffe, Andrew ^{[14
]}

Bis, Joshua C. M. ^{[16
]}

Verwoert, Germaine C. ^{[6
,7
,22
]}

Teumer, Alexander ^{[23
]}

Fox, Caroline S. ^{[2
,12
]}

Guralnik, Jack M. ^{[24
]}

Ehret, Georg B. ^{[3
,25
]}

Rice, Kenneth ^{[26
]}

Felix, Janine F. ^{[6
,7
]}

Rendon, Augusto ^{[27
,28
]}

Eiriksdottir, Gudny ^{[10
]}

Levy, Daniel ^{[2
,12
]}

Patel, Kushang V. ^{[24
]}

Boerwinkle, Eric ^{[29
]}

Rotter, Jerome I. ^{[30
]}

Hofman, Albert ^{[6
,7
]}

Sambrook, Jennifer G. ^{[27
,28
]}

Hernandez, Dena G. ^{[11
]}

Zheng, Gang ^{[31
]}

Bandinelli, Stefania ^{[32
]}

Singleton, Andrew B.

Coresh, Josef ^{[14
]}

Lumley, Thomas ^{[26
]}

Uitterlinden, Andre G. ^{[6
,7
,22
,33
]}

vanGils, Janine M.

Launer, Lenore J. ^{[24
]}

Cupples, L. Adrienne ^{[9
,12
]}

Oostra, Ben A. ^{[6
,7
,35
]}

Zwaginga, Jaap-Jan ^{[34
,36
]}

Ouwehand, Willem H. ^{[8
,27
,28
]}

Thein, Swee-Lay ^{[37
]}

Meisinger, Christa ^{[17
]}

Deloukas, Panos ^{[8
]}

Nauck, Matthias ^{[38
]}

Spector, Tim D. ^{[9
]}

Gieger, Christian ^{[17
]}

机构：

[1] NHGRI, Div Intramural Res, Bethesda, MD 20892 USA

[2] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA

[3] Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Baltimore, MD USA

[4] Univ Vermont, Dept Med, Burlington, VT USA

[5] Univ Vermont, Dept Pathol, Burlington, VT 05405 USA

[6] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands

[7] NCHA, NGI, Leiden, Netherlands

[8] Wellcome Trust Sanger Inst, Hinxton, England

[9] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England

[10] Iceland Heart Assoc, Kopavogur, Iceland

[11] NIA, Intramural Res Program, Neurogenet Lab, NIH, Bethesda, MD 20892 USA

[12] NHLBIs Framingham Heart Study, Framingham, MA USA

[13] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA

[14] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA

[15] Univ Washington, Dept Med, Seattle, WA USA

[16] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA

[17] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, Neuherberg, Germany

[18] Univ Iceland, Reykjavik, Iceland

[19] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA

[20] NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA

[21] MedStar Res Inst, Hyattsville, MD USA

[22] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands

[23] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany

[24] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA

[25] Univ Hosp Geneva, Ctr Cardiol, Geneva, Switzerland

[26] Univ Washington, Dept Biostat, Seattle, WA 98195 USA

[27] Univ Cambridge, Dept Haematol, Cambridge, England

[28] Natl Hlth Serv Blood & Transplant, Cambridge, England

[29] Univ Texas Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA

[30] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA

[31] NHLBI, Off Biostat Res, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA

[32] Geriatr Unit ASF, Florence, Italy

[33] Erasmus MC, Dept Clin Chem, Rotterdam, Netherlands

[34] Leiden Univ, Med Ctr, Dept Immunohematol & Blood Transfus, Leiden, Netherlands

[35] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands

[36] Sanquin Res, Dept Expt Immunohematol, Amsterdam, Netherlands

[37] Kings Coll London, Dept Haematol, London WC2R 2LS, England

[38] Ernst Moritz Arndt Univ Greifswald, Inst Klin Chem & Lab Med, Greifswald, Germany

[39] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA

[40] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA

[41] Grp Hlth, Grp Hlth Res Inst, Seattle, WA USA

[42] Ernst Moritz Arndt Univ Greifswald, Inst Immunol & Transfus Med, Greifswald, Germany

[43] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA

[44] Johns Hopkins Sch Med, Dept Pediat, Baltimore, MD USA

来源：

NATURE GENETICS | 2009年 / 41卷 / 11期

基金：

英国医学研究理事会;

关键词：

GENOME-WIDE ASSOCIATION; BLOOD-PRESSURE; HEMOGLOBIN CONCENTRATION; HEMOCHROMATOSIS GENE; HEREDITARY HEMOCHROMATOSIS; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; FETAL-HEMOGLOBIN; CELIAC-DISEASE; C-MYB;

D O I：

10.1038/ng.466

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：1191 / U48

页数：10

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