Abstract
The number and volume of cells in the blood affect a wide range of disorders including cancer and cardiovascular, metabolic, infectious and immune conditions. We consider here the genetic variation in eight clinically relevant hematological parameters, including hemoglobin levels, red and white blood cell counts and platelet counts and volume. We describe common variants within 22 genetic loci reproducibly associated with these hematological parameters in 13,943 samples from six European population-based studies, including 6 associated with red blood cell parameters, 15 associated with platelet parameters and 1 associated with total white blood cell count. We further identified a long-range haplotype at 12q24 associated with coronary artery disease and myocardial infarction in 9,479 cases and 10,527 controls. We show that this haplotype demonstrates extensive disease pleiotropy, as it contains known risk loci for type 1 diabetes, hypertension and celiac disease and has been spread by a selective sweep specific to European and geographically nearby populations.
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Acknowledgements
The Wellcome Trust, EU (HEALTH-F2-2008-ENGAGE, QLG2-CT-2002-01254), National Institute for Health Research of England (NIHR) (TwinsUK); The Wellcome Trust (UKBS-CC1); Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany, the German Federal Ministry of Education and Research (BMBF), the German National Genome Research Network (NGFN), Munich Center of Health Sciences (MC Health) (KORA); Federal Ministry of Education and Research (grants no. 01ZZ9603, 01ZZ0103 and 01ZZ0403), Ministry of Cultural Affairs, Social Ministry of the Federal State of Mecklenburg-West Pomerania, Deutsche Forschungsgemeinschaft (grant SFB TR 19), the Federal Ministry of Education and Research (grant no. 03ZIK012); a joint grant from Siemens Healthcare, Erlangen, Germany and the Federal State of Mecklenburg-West Pomerania (SHIP); NIHR, CBMRC, NHSBT, (CBR); Deutsche Forschungsgemeinschaft, the German Federal Ministry of Education and Research (BMBF) (NGFN-2 and NGFN-plus), EU (LSHM-CT-2006-037593) (GerMIFS I and II); BHF and the UK MRC, the Wellcome Trust, Leicester NIHR Biomedical Research Unit in Cardiovascular Disease and EU-FP6 (LSHM-CT-2004-503485) (WTCCC-CAD); Cardiovascular Institute (University of Pennsylvania), GlaxoSmithKline, MedSTAR Research Institute (PennCATH/MedSTAR); US National Institutes of Health (NIH) and National Heart, Lung, and Blood Institute (STAMPEED), National Center for Research Resource (U54 RR020278) (MIGen); Canadian Institutes of Health Research (MOP82810, NA6650 and MOP77682), Canada Foundation for Innovation and Ontario Research Foundation (#11966) (OHGS); Finnish Foundation for Cardiovascular Research, Sigrid Juselius Foundation (COROGENE); Juvenile Diabetes Research Foundation/Wellcome Trust (T1D).
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Manuscript preparation: N.S., M.M., A.R., W.H.O., T.D.S., P.D., N.J.S. and C.G.
Main data analysis: N.S., C.G., B.K., A.R., A.T., R.A.L., Y.X. and C.T.-S. Intermediate trait analysis cohorts. Study design and biobanking: T.D.S. (TwinsUK), J.R.B., W.E., S.F.G., J.S.-C., J. Sambrook, N.A.W., W.H.O. (UKBS-CC1 and CBR), C.G., T.I., H.-E.W. (KORA F3 and F4), M.N., U.V. and H.V. (SHIP). Phenotype assessment: S.M., M.F., S.L.T., T.D.S. (TwinsUK), A.D., C.M. (KORA F3 and F4) and A.G. (SHIP). Genotyping: R.G., S.C.P., C.M.R., P.D. (TwinsUK), S.B., M.J.R.G., R.G., N.H., J. Stephens (CBR), H.P. and T.I. (KORA F3 and F4). Statistical analysis: N.S. (TwinsUK, CBR and UKBS-CC1), C.G, B.K. (KORA F3 and F4), A.T. (SHIP), A.R. and P.B. (Transcriptomics). CAD/MI cohorts. GerMIFS I and GerMIFS II: C.H., I.R.K., S.S., K.S., C.W., H.-E.W., C.W., J.E., H.S. WTCCC-CAD: N.J.S., A.H.G., A.S.H., B.W. and J.R.T. Ottawa Heart Study: L.C., R.M., R.R., G.A.W. and A.F.R.S. PennCATH/MedSTAR: M.L., M.S.B., J.D., S.E.E., H.H.H., D.J.R., M.P.R., V.M. and C.W.K. MIGEN: S.K., B.F.V., S.M.S., V.S., R.E., O.M., C.J.O., L.P., D.S.S. and D.A. COROGENE: M.P., P.S., V.S., L.P., I.S., J. Sinisalo and M.S.N. Celiac disease. D.A.v.H.
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Soranzo, N., Spector, T., Mangino, M. et al. A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium. Nat Genet 41, 1182–1190 (2009). https://doi.org/10.1038/ng.467
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DOI: https://doi.org/10.1038/ng.467
