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. 2009 Nov;41(11):1191-8.
doi: 10.1038/ng.466. Epub 2009 Oct 11.

Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium

Santhi K Ganesh  1 , Neil A Zakai, Frank J A van Rooij, Nicole Soranzo, Albert V Smith, Michael A Nalls, Ming-Huei Chen, Anna Kottgen, Nicole L Glazer, Abbas Dehghan, Brigitte Kuhnel, Thor Aspelund, Qiong Yang, Toshiko Tanaka, Andrew Jaffe, Joshua C M Bis, Germaine C Verwoert, Alexander Teumer, Caroline S Fox, Jack M Guralnik, Georg B Ehret, Kenneth Rice, Janine F Felix, Augusto Rendon, Gudny Eiriksdottir, Daniel Levy, Kushang V Patel, Eric Boerwinkle, Jerome I Rotter, Albert Hofman, Jennifer G Sambrook, Dena G Hernandez, Gang Zheng, Stefania Bandinelli, Andrew B Singleton, Josef Coresh, Thomas Lumley, André G Uitterlinden, Janine M Vangils, Lenore J Launer, L Adrienne Cupples, Ben A Oostra, Jaap-Jan Zwaginga, Willem H Ouwehand, Swee-Lay Thein, Christa Meisinger, Panos Deloukas, Matthias Nauck, Tim D Spector, Christian Gieger, Vilmundur Gudnason, Cornelia M van Duijn, Bruce M Psaty, Luigi Ferrucci, Aravinda Chakravarti, Andreas Greinacher, Christopher J O'Donnell, Jacqueline C M Witteman, Susan Furth, Mary Cushman, Tamara B Harris, Jing-Ping Lin
Affiliations

Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium

Santhi K Ganesh et al. Nat Genet. 2009 Nov.

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.

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Figures

Figure 1
Figure 1
Overview of CHARGE meta-analysis results for six erythrocyte traits: hemoglobin concentration (Hgb), hematocrit (Hct), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV), erythrocyte count (RBC). -log10 (P value) is plotted on the y-axis against genomic position of each SNP. Genomic loci with significant association (P < 5 × 10-8) are plotted in red, and loci with suggestive evidence are in blue (P < 4 × 10-7).
Figure 2
Figure 2
Results of the CHARGE meta-analysis are organized into a Venn diagram, demonstrating overlap of loci meeting a genome-wide significance threshold of P < 5×10-8.
Figure 3
Figure 3
Gene expression in blood and endothelial cells for genes in the chromosome 6q23.3 region. (a) SNPs in the locus are plotted against recombination rates as observed in HapMap CEU, using a window of +/-500kb around the lead SNP identified in this locus, which is plotted in blue. SNPs identified by the CHARGE meta-analyses are colored according to correlation with the lead SNP (r2 ≥ 0.8 red; 0.5 ≤ r2 < 0.8 orange; 0.2 ≤ r2 < 0.5 yellow; r2 < 0.2 white; no r2 value provided). The P value for the lead SNP in this region is provided. (b) A heatmap of gene expression levels in nine blood and endothelial cell lines is shown, including all genes, as annotated by ENSEMBL 54, within the +/- 500kb window of the locus (MK = megakaryocyte; EB = erythroid bodies; HUVEC = human umbilical vein endothelial cells; CD14 = monocytes; CD66b = granulocytes; CD19 = B lymphocytes; CD56 = NK cells; CD8 = Tc lymphocytes; CD4 = Th lymphocytes).
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References

    1. Havlik RJ, et al. Evidence for additional blood pressure correlates in adults 20-56 years old. Circulation. 1980;61:710–5. - PubMed
    1. Tell GS, et al. The Cardiovascular Health Study. Cardiovascular Health Study (CHS) Collaborative Research Group Correlates of blood pressure in community-dwelling older adults. Hypertension. 1994;23:59–67. - PubMed
    1. Zakai NA, et al. A prospective study of anemia status, hemoglobin concentration, and mortality in an elderly cohort: the Cardiovascular Health Study. Arch Intern Med. 2005;165:2214–20. - PubMed
    1. Whitfield JB, Martin NG. Genetic and environmental influences on the size and number of cells in the blood. Genet Epidemiol. 1985;2:133–44. - PubMed
    1. Evans DM, Frazer IH, Martin NG. Genetic and environmental causes of variation in basal levels of blood cells. Twin Res. 1999;2:250–7. - PubMed