Article | Published:

Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium

Nature Genetics volume 41, pages 11911198 (2009) | Download Citation


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.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1.

    et al. Evidence for additional blood pressure correlates in adults 20–56 years old. Circulation 61, 710–715 (1980).

  2. 2.

    et al. Correlates of blood pressure in community-dwelling older adults. The Cardiovascular Health Study. Cardiovascular Health Study (CHS) Collaborative Research Group. Hypertension 23, 59–67 (1994).

  3. 3.

    et al. A prospective study of anemia status, hemoglobin concentration, and mortality in an elderly cohort: the Cardiovascular Health Study. Arch. Intern. Med. 165, 2214–2220 (2005).

  4. 4.

    & Genetic and environmental influences on the size and number of cells in the blood. Genet. Epidemiol. 2, 133–144 (1985).

  5. 5.

    , & Genetic and environmental causes of variation in basal levels of blood cells. Twin Res. 2, 250–257 (1999).

  6. 6.

    et al. Evidence for linkage of red blood cell size and count: genome-wide scans in the Framingham Heart Study. Am. J. Hematol. 82, 605–610 (2007).

  7. 7.

    et al. Determinants and characteristics of mean corpuscular volume and hemoglobin concentration in white HFE C282Y homozygotes in the hemochromatosis and iron overload screening study. Am. J. Hematol. 82, 898–905 (2007).

  8. 8.

    , , & Etiology of differences in hematocrit between males and females: sequence-based polymorphisms in erythropoietin and its receptor. J. Gend. Specif. Med. 4, 35–40 (2001).

  9. 9.

    , , & Sequence-based polymorphisms in members of the apoptosis Bcl-2 gene family and their association with hematocrit level. J. Gend. Specif. Med. 6, 36–42 (2003).

  10. 10.

    et al. The HBS1L-MYB intergenic region on chromosome 6q23.3 influences erythrocyte, platelet, and monocyte counts in humans. Blood 110, 3624–3626 (2007).

  11. 11.

    et al. Genomewide scans of red cell indices suggest linkage on chromosome 6q23. J. Med. Genet. 44, 24–30 (2007).

  12. 12.

    , , , & Genome-wide association and linkage analyses of hemostatic factors and hematological phenotypes in the Framingham Heart Study. BMC Med. Genet. 8 (Suppl. 1), S12 (2007).

  13. 13.

    , , & Evidence for a gene influencing haematocrit on chromosome 6q23–24: genomewide scan in the Framingham Heart Study. J. Med. Genet. 42, 75–79 (2005).

  14. 14.

    et al. Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium: design of prospective meta-analyses of genome-wide association studies from five cohorts. Circ. Cardiovasc. Genet. 2, 73–80 (2009).

  15. 15.

    et al. Genome-wide association study of blood pressure and hypertension. Nat. Genet. 41, 677–687 (2009).

  16. 16.

    , , , & Partial deficiency of erythrocyte spectrin in hereditary spherocytosis. Nature 314, 380–383 (1985).

  17. 17.

    et al. Mutant forms of spectrin alpha-subunits in hereditary elliptocytosis. J. Clin. Invest. 80, 191–198 (1987).

  18. 18.

    et al. A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nat. Genet. 13, 399–408 (1996).

  19. 19.

    et al. Heterozygosity for a hereditary hemochromatosis gene is associated with cardiovascular death in women. Circulation 100, 1268–1273 (1999).

  20. 20.

    et al. Increased risk of acute myocardial infarction in carriers of the hemochromatosis gene Cys282Tyr mutation: a prospective cohort study in men in eastern Finland. Circulation 100, 1274–1279 (1999).

  21. 21.

    et al. ER stress controls iron metabolism through induction of hepcidin. Science 325, 877–880 (2009).

  22. 22.

    & Hepcidin: a new tool in the management of anaemia in patients with chronic kidney disease? Nephrol. Dial. Transplant. 23, 2450–2453 (2008).

  23. 23.

    et al. Hepcidin antimicrobial peptide transgenic mice exhibit features of the anemia of inflammation. Blood 109, 4038–4044 (2007).

  24. 24.

    et al. The hemochromatosis gene product complexes with the transferrin receptor and lowers its affinity for ligand binding. Proc. Natl. Acad. Sci. USA 95, 1472–1477 (1998).

  25. 25.

    et al. Mutations in TMPRSS6 cause iron-refractory iron deficiency anemia (IRIDA). Nat. Genet. 40, 569–571 (2008).

  26. 26.

    et al. Stat5 regulates cellular iron uptake of erythroid cells via IRP-2 and TfR-1. Blood 112, 3878–3888 (2008).

  27. 27.

    et al. Hemochromatosis due to mutations in transferrin receptor 2. Blood Cells Mol. Dis. 29, 465–470 (2002).

  28. 28.

    et al. Genome-wide association study shows BCL11A associated with persistent fetal hemoglobin and amelioration of the phenotype of beta-thalassemia. Proc. Natl. Acad. Sci. USA 105, 1620–1625 (2008).

  29. 29.

    et al. A QTL influencing F cell production maps to a gene encoding a zinc-finger protein on chromosome 2p15. Nat. Genet. 39, 1197–1199 (2007).

  30. 30.

    et al. Diffuse large B-cell lymphoma subgroups have distinct genetic profiles that influence tumor biology and improve gene-expression-based survival prediction. Blood 106, 3183–3190 (2005).

  31. 31.

    et al. Human fetal hemoglobin expression is regulated by the developmental stage-specific repressor BCL11A. Science 322, 1839–1842 (2008).

  32. 32.

    & Genetic complexity in sickle cell disease. Proc. Natl. Acad. Sci. USA 105, 11595–11596 (2008).

  33. 33.

    et al. c-Myb and p300 regulate hematopoietic stem cell proliferation and differentiation. Dev. Cell 8, 153–166 (2005).

  34. 34.

    et al. Progression through key stages of haemopoiesis is dependent on distinct threshold levels of c-Myb. EMBO J. 22, 4478–4488 (2003).

  35. 35.

    et al. Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction. Nat. Genet. 41, 342–347 (2009).

  36. 36.

    et al. Genome-wide association study identifies eight loci associated with blood pressure. Nat. Genet. 41, 666–676 (2009).

  37. 37.

    et al. Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes. Nat. Genet. 39, 857–864 (2007).

  38. 38.

    et al. Newly identified genetic risk variants for celiac disease related to the immune response. Nat. Genet. 40, 395–402 (2008).

  39. 39.

    et al. Shared and distinct genetic variants in type 1 diabetes and celiac disease. N. Engl. J. Med. 359, 2767–2777 (2008).

  40. 40.

    et al. Cytokine signaling and hematopoietic homeostasis are disrupted in Lnk-deficient mice. J. Exp. Med. 195, 1599–1611 (2002).

  41. 41.

    et al. Abnormal mesoderm patterning in mouse embryos mutant for the SH2 tyrosine phosphatase Shp-2. EMBO J. 16, 2352–2364 (1997).

  42. 42.

    et al. Genotypic and phenotypic characterization of Noonan syndrome: new data and review of the literature. Am. J. Med. Genet. A. 134A, 165–170 (2005).

  43. 43.

    et al. Genetic heterogeneity in LEOPARD syndrome: two families with no mutations in PTPN11. J. Hum. Genet. 50, 21–25 (2005).

  44. 44.

    et al. Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, myelodysplastic syndromes and acute myeloid leukemia. Nat. Genet. 34, 148–150 (2003).

  45. 45.

    et al. Promoter polymorphism of the erythropoietin gene in severe diabetic eye and kidney complications. Proc. Natl. Acad. Sci. USA 105, 6998–7003 (2008).

  46. 46.

    & Haematocrit: relationships with blood lipids, blood pressure and other cardiovascular risk factors. Thromb. Haemost. 72, 58–64 (1994).

  47. 47.

    , , & Hematocrit and the risk of cardiovascular disease—the Framingham study: a 34-year follow-up. Am. Heart J. 127, 674–682 (1994).

  48. 48.

    , , & Mortality and anaemia in women. Lancet 1, 891–894 (1974).

  49. 49.

    et al. Anemia as a risk factor for cardiovascular disease in The Atherosclerosis Risk in Communities (ARIC) study. J. Am. Coll. Cardiol. 40, 27–33 (2002).

  50. 50.

    et al. Association of blood pressure with blood viscosity in american indians: the Strong Heart Study. Hypertension 45, 625–630 (2005).

  51. 51.

    , , & Elevated blood viscosity in patients with borderline essential hypertension. Hypertension 5, 757–762 (1983).

  52. 52.

    et al. Mean red cell volume as a correlate of blood pressure. Circulation 93, 1677–1684 (1996).

  53. 53.

    & Influence of flow properties of blood upon viscosity-hematocrit relationships. J. Clin. Invest. 41, 1591–1598 (1962).

  54. 54.

    , & High blood viscosity syndrome in cerebral infarction. Stroke 5, 330–333 (1974).

  55. 55.

    et al. Identification of a gene responsible for familial Wolff-Parkinson-White syndrome. N. Engl. J. Med. 344, 1823–1831 (2001).

  56. 56.

    et al. Novel PRKAG2 mutation responsible for the genetic syndrome of ventricular preexcitation and conduction system disease with childhood onset and absence of cardiac hypertrophy. Circulation 104, 3030–3033 (2001).

  57. 57.

    & The definition of anemia: what is the lower limit of normal of the blood hemoglobin concentration? Blood 107, 1747–1750 (2006).

  58. 58.

    & Imputation-based analysis of association studies: candidate regions and quantitative traits. PLoS Genet. 3, e114 (2007).

  59. 59.

    et al. Principal components analysis corrects for stratification in genome-wide association studies. Nat. Genet. 38, 904–909 (2006).

  60. 60.

    & Genomic control for association studies. Biometrics 55, 997–1004 (1999).

  61. 61.

    et al. A HaemAtlas: characterizing gene expression in differentiated human blood cells. Blood 113, e1–e9 (2009).

  62. 62.

    et al. P-selectin glycoprotein ligand-1 is expressed on endothelial cells and mediates monocyte adhesion to activated endothelium. Arterioscler. Thromb. Vasc. Biol. 27, 1023–1029 (2007).

  63. 63.

    , & lumi: a pipeline for processing Illumina microarray. Bioinformatics 24, 1547–1548 (2008).

  64. 64.

    (ed.). Online Mendelian Inheritance in Man (McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University (Baltimore, Maryland, USA) and National Center for Biotechnology Information, National Library of Medicine (Bethesda, Maryland, USA)). <>.

  65. 65.

    , , & The genetic association database. Nat. Genet. 36, 431–432 (2004).

Download references


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

Author notes

    • Santhi K Ganesh
    • , Neil A Zakai
    • , Frank J A van Rooij
    • , Nicole Soranzo
    • , Albert V Smith
    • , Michael A Nalls
    • , Andreas Greinacher
    • , Christopher J O'Donnell
    • , Jacqueline C M Witteman
    • , Susan Furth
    • , Mary Cushman
    • , Tamara B Harris
    •  & Jing-Ping Lin

    These authors contributed equally to this work.


  1. National Human Genome Research Institute, Division of Intramural Research, Bethesda, Maryland, USA.

    • Santhi K Ganesh
  2. National Heart, Lung, and Blood Institute (NHLBI), Division of Intramural Research, Bethesda, Maryland, USA.

    • Santhi K Ganesh
    • , Caroline S Fox
    • , Daniel Levy
    •  & Christopher J O'Donnell
  3. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, Maryland, USA.

    • Santhi K Ganesh
    • , Georg B Ehret
    •  & Aravinda Chakravarti
  4. Departments of Medicine and Pathology, University of Vermont, Burlington, Vermont, USA.

    • Neil A Zakai
    •  & Mary Cushman
  5. Department of Epidemiology, Erasmus Medical Center (MC), Rotterdam, The Netherlands.

    • Frank J A van Rooij
    • , Abbas Dehghan
    • , Germaine C Verwoert
    • , Janine F Felix
    • , Albert Hofman
    • , André G Uitterlinden
    • , Ben A Oostra
    • , Cornelia M van Duijn
    •  & Jacqueline C M Witteman
  6. The Netherlands Genomics Initiative–sponsored Netherlands Consortium for Healthy Aging (NGI-NCHA), Leiden, The Netherlands.

    • Frank J A van Rooij
    • , Abbas Dehghan
    • , Germaine C Verwoert
    • , Janine F Felix
    • , Albert Hofman
    • , André G Uitterlinden
    • , Ben A Oostra
    • , Cornelia M van Duijn
    •  & Jacqueline C M Witteman
  7. Human Genetics, Wellcome Trust Sanger Institute, Genome Campus, Hinxton, UK.

    • Nicole Soranzo
    • , Willem H Ouwehand
    •  & Panos Deloukas
  8. Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.

    • Nicole Soranzo
    • , L Adrienne Cupples
    •  & Tim D Spector
  9. Icelandic Heart Association, Kopavogur, Iceland.

    • Albert V Smith
    • , Thor Aspelund
    • , Gudny Eiriksdottir
    •  & Vilmundur Gudnason
  10. Laboratory of Neurogenetics, National Institute of Aging (NIA), National Institutes of Health (NIH), Bethesda, Maryland, USA.

    • Michael A Nalls
    •  & Andrew B Singleton
  11. NHLBI's Framingham Heart Study, Framingham, Massachusetts, USA.

    • Ming-Huei Chen
    • , Qiong Yang
    • , Caroline S Fox
    • , Daniel Levy
    • , L Adrienne Cupples
    •  & Christopher J O'Donnell
  12. Department of Neurology, Boston University School of Medicine, Boston, Massachusetts, USA.

    • Ming-Huei Chen
  13. Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland, USA.

    • Anna Kottgen
    • , Andrew Jaffe
    •  & Josef Coresh
  14. Department of Medicine, University of Washington, Seattle, Washington, USA.

    • Nicole L Glazer
    •  & Bruce M Psaty
  15. Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, USA.

    • Nicole L Glazer
    • , Joshua C M Bis
    •  & Bruce M Psaty
  16. Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.

    • Brigitte Kuhnel
    • , Christa Meisinger
    •  & Christian Gieger
  17. University of Iceland, Reykjavik, Iceland.

    • Thor Aspelund
    •  & Vilmundur Gudnason
  18. Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.

    • Qiong Yang
  19. Longitudinal Studies Section–Clinical Research Branch, NIA, NIH, Baltimore, Maryland, USA.

    • Toshiko Tanaka
    •  & Luigi Ferrucci
  20. MedStar Research Institute, Hyattsville, Maryland, USA.

    • Toshiko Tanaka
  21. Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.

    • Germaine C Verwoert
    •  & André G Uitterlinden
  22. Interfaculty Institute for Genetics and Functional Genomics, Ernst-Moritz-Arndt-Universität Greifswald, Greifswald, Germany.

    • Alexander Teumer
  23. Laboratory for Epidemiology, Demography, and Biometry, NIA, NIH, Bethesda, Maryland, USA.

    • Jack M Guralnik
    • , Kushang V Patel
    • , Lenore J Launer
    •  & Tamara B Harris
  24. Cardiology Center, Geneva University Hospital, Geneva, Switzerland.

    • Georg B Ehret
  25. Department of Biostatistics, University of Washington, Seattle, Washington, USA.

    • Kenneth Rice
    •  & Thomas Lumley
  26. Department of Haematology, University of Cambridge and National Health Service Blood and Transplant, Long Road, Cambridge, UK.

    • Augusto Rendon
    • , Jennifer G Sambrook
    •  & Willem H Ouwehand
  27. Human Genetics Center, University of Texas Health Science Center, Houston, Texas, USA.

    • Eric Boerwinkle
  28. Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.

    • Jerome I Rotter
  29. Intramural Research Program, Laboratory of Neurogenetics, NIA, NIH, Bethesda, Maryland, USA.

    • Dena G Hernandez
  30. Office of Biostatistical Research, Division of Cardiovascular Sciences, NHLBI, NIH, Bethesda, Maryland, USA.

    • Gang Zheng
    •  & Jing-Ping Lin
  31. Geriatric Unit ASF, Firenze, Italy.

    • Stefania Bandinelli
  32. Department of Clinical Chemistry, Erasmus Medical Center, Rotterdam, The Netherlands.

    • André G Uitterlinden
  33. Leiden University Medical Center, Leiden, The Netherlands.

    • Janine M vanGils
  34. Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.

    • Ben A Oostra
  35. Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.

    • Jaap-Jan Zwaginga
  36. Department of Experimental Immunohematology, Sanquin Research, Amsterdam, The Netherlands.

    • Jaap-Jan Zwaginga
  37. Department of Haematology, King's College London, London, UK.

    • Swee-Lay Thein
  38. Institut für Klinische Chemie und Laboratoriumsmedizin, Ernst-Moritz-Arndt Universität Greifswald, Greifswald, Germany.

    • Matthias Nauck
  39. Department of Epidemiology, University of Washington, Seattle, Washington, USA.

    • Bruce M Psaty
  40. Department of Health Services, University of Washington, Seattle, Washington, USA.

    • Bruce M Psaty
  41. Group Health Research Institute, Group Health, Seattle, Washington, USA.

    • Bruce M Psaty
  42. Institut für Immunologie und Transfusionsmedizin, Ernst-Moritz-Arndt-Universität Greifswald, Greifswald, Germany.

    • Andreas Greinacher
  43. Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.

    • Christopher J O'Donnell
  44. Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.

    • Susan Furth


  1. Search for Santhi K Ganesh in:

  2. Search for Neil A Zakai in:

  3. Search for Frank J A van Rooij in:

  4. Search for Nicole Soranzo in:

  5. Search for Albert V Smith in:

  6. Search for Michael A Nalls in:

  7. Search for Ming-Huei Chen in:

  8. Search for Anna Kottgen in:

  9. Search for Nicole L Glazer in:

  10. Search for Abbas Dehghan in:

  11. Search for Brigitte Kuhnel in:

  12. Search for Thor Aspelund in:

  13. Search for Qiong Yang in:

  14. Search for Toshiko Tanaka in:

  15. Search for Andrew Jaffe in:

  16. Search for Joshua C M Bis in:

  17. Search for Germaine C Verwoert in:

  18. Search for Alexander Teumer in:

  19. Search for Caroline S Fox in:

  20. Search for Jack M Guralnik in:

  21. Search for Georg B Ehret in:

  22. Search for Kenneth Rice in:

  23. Search for Janine F Felix in:

  24. Search for Augusto Rendon in:

  25. Search for Gudny Eiriksdottir in:

  26. Search for Daniel Levy in:

  27. Search for Kushang V Patel in:

  28. Search for Eric Boerwinkle in:

  29. Search for Jerome I Rotter in:

  30. Search for Albert Hofman in:

  31. Search for Jennifer G Sambrook in:

  32. Search for Dena G Hernandez in:

  33. Search for Gang Zheng in:

  34. Search for Stefania Bandinelli in:

  35. Search for Andrew B Singleton in:

  36. Search for Josef Coresh in:

  37. Search for Thomas Lumley in:

  38. Search for André G Uitterlinden in:

  39. Search for Janine M vanGils in:

  40. Search for Lenore J Launer in:

  41. Search for L Adrienne Cupples in:

  42. Search for Ben A Oostra in:

  43. Search for Jaap-Jan Zwaginga in:

  44. Search for Willem H Ouwehand in:

  45. Search for Swee-Lay Thein in:

  46. Search for Christa Meisinger in:

  47. Search for Panos Deloukas in:

  48. Search for Matthias Nauck in:

  49. Search for Tim D Spector in:

  50. Search for Christian Gieger in:

  51. Search for Vilmundur Gudnason in:

  52. Search for Cornelia M van Duijn in:

  53. Search for Bruce M Psaty in:

  54. Search for Luigi Ferrucci in:

  55. Search for Aravinda Chakravarti in:

  56. Search for Andreas Greinacher in:

  57. Search for Christopher J O'Donnell in:

  58. Search for Jacqueline C M Witteman in:

  59. Search for Susan Furth in:

  60. Search for Mary Cushman in:

  61. Search for Tamara B Harris in:

  62. Search for Jing-Ping Lin in:


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.

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.

Corresponding authors

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

Supplementary information

PDF files

  1. 1.

    Supplementary Text and Figures

    Supplementary Tables 1, 2, 4 and 5, Supplementary Figures 1 and 2, and Supplementary Note

Excel files

  1. 1.

    Supplementary Table 3

    All CHARGE meta analysis results.

About this article

Publication history





Further reading