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Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium


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 × 10−8 to 7 × 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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Figure 1: Overview of CHARGE meta-analysis results for six erythrocyte traits: hemoglobin concentration (Hb), hematocrit (Hct), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV) and erythrocyte count (RBC).
Figure 2
Figure 3: Gene expression in blood and endothelial cells for genes in the chromosome 6q23.3 region.


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Complete study acknowledgments are listed in the Supplementary Note. The authors thank the studies' participants and staff and the funding agencies for their support.

Author information




AGES: Study design and phenotype collection, T.B.H.,V.G., L.J.L., G.E.; data analysis, A.V.S., M.A.N., T.A.; manuscript preparation, M.A.N., N.S.; manuscript revisions, T.B.H.,V.G., L.J.L., A.V.S., A.B.S., D.G.H., M.A.N. ARIC: Study design and phenotype collection, E.B., J.C., S.F., A.C.; genotyping, E.B., A.C.; data analysis, S.K.G., A.K., A.C., A.G., G.B.E., A.J.; manuscript preparation, S.K.G., S.F.; manuscript revisions, S.K.G., A.C., E.B., J.C., A.K., S.F. CHS: Study design and phenotype collection, B.M.P., J.I.R., M.C., N.A.Z., N.L.G.; genotyping, J.I.R.; data analysis, N.L.G, T.L.; manuscript preparation, N.A.Z.; manuscript revisions, B.M.P., J.C.M.B., K.R., J.I.R., M.C., N.A.Z., N.L.G., T.L. FHS: Study design and phenotype collection, M.-H.C., Q.Y., C.S.F., D.L., L.A.C., C.J.O., J.-P.L.; data analysis, M.-H.C., Q.Y., J.-P.L., G.Z.; manuscript preparation, M.-H.C., C.J.O., J.-P.L.; manuscript revisions, M.-H.C., Q.Y., C.S.F., D.L., L.A.C., C.J.O., J.-P.L. Rotterdam: Study design and phenotype collection, F.J.A.v.R., A.H., A.G.U., B.A.O., C.M.v.D., J.C.M.W.; genotyping, A.G.U.; data analysis, F.J.A.v.R., J.F.F., A.D., G.C.V.; manuscript preparation, F.J.A.v.R., J.F.F., C.M.v.D.; manuscript revisions, F.J.A.v.R., J.F.F., A.D., G.C.V., A.H., A.G.U., B.A.O., C.M.v.D., J.C.M.W. InCHIANTI: Study design and phenotype collection, L.F., J.M.G., S.B.; data analysis, M.A.N., T.T.; manuscript preparation, M.A.N.; manuscript revisions, L.F., J.M.G., S.B., K.V.P., A.B.S., D.G.H., M.A.N., T.T. HaemGen: A.R., J.-J.Z., J.M.vG. Twins UK: Study design and phenotype collection, T.D.S., S.-L.T., P.D.; data analysis and manuscript preparation and revisions, N.S. UKBS1: Study design and phenotype collection, W.H.O., J.G.S.; data analysis, N.S.; manuscript preparation and revisions, N.S., A.R. KORA: Study design and phenotype collection, C.M., C.G.; data analysis, C.G., B.K.; manuscript preparation and revisions, C.G. SHIP: Study design and phenotype collection, M.N., A.G.; data analysis, A.T.; gene expression, A.R., J.-J.Z., J.M.vG.

Corresponding authors

Correspondence to Santhi K Ganesh or Christopher J O'Donnell.

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Competing interests

A. Chakravarti is a paid member of the Scientific Advisory Boards of Affymetrix and Pyxis Genomics. These potential conflicts of interest are managed by the policies of Johns Hopkins University School of Medicine.

Supplementary information

Supplementary Text and Figures

Supplementary Tables 1, 2, 4 and 5, Supplementary Figures 1 and 2, and Supplementary Note (PDF 3493 kb)

Supplementary Table 3

All CHARGE meta analysis results. (XLS 288 kb)

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Ganesh, S., Zakai, N., van Rooij, F. et al. Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium. Nat Genet 41, 1191–1198 (2009).

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