A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium

Nicole Soranzo; Tim D. Spector; Massimo Mangino; Brigitte Kühnel; Augusto Rendon; Alexander Teumer; Christina Willenborg; Benjamin Wright; Li Chen; Mingyao Li; Perttu Salo; Benjamin F. Voight; Philippa Burns; Roman A. Laskowski; Yali Xue; Stephan Menzel; David Altshuler; John R. Bradley; Suzannah Bumpstead; Mary Susan Burnett; Joseph Devaney; Angela Döring; Roberto Elosua; Stephen E. Epstein; Wendy Erber; Mario Falchi; Stephen F. Garner; Mohammed J.R. Ghori; Alison H. Goodall; Rhian Gwilliam; Hakon H. Hakonarson; Alistair S. Hall; Naomi Hammond; Christian Hengstenberg; Thomas Illig; Inke R. König; Christopher W. Knouff; Ruth McPherson; Olle Melander; Vincent Mooser; Matthias Nauck; Markku S. Nieminen; Christopher J. O'Donnell; Leena Peltonen; Simon C. Potter; Holger Prokisch; Daniel J. Rader; Catherine M. Rice; Robert Roberts; Veikko Salomaa; Jennifer Sambrook; Stefan Schreiber; Heribert Schunkert; Stephen M. Schwartz; Jovana Serbanovic-Canic; Juha Sinisalo; David S. Siscovick; Klaus Stark; Ida Surakka; Jonathan Stephens; John R. Thompson; Uwe Völker; Henry Völzke; Nicholas A. Watkins; George A. Wells; H. Erich Wichmann; David A. Van Heel; Chris Tyler-Smith; Swee Lay Thein; Sekar Kathiresan; Markus Perola; Muredach P. Reilly; Alexandre F.R. Stewart; Jeanette Erdmann; Nilesh J. Samani; Christa Meisinger; Andreas Greinacher; Panos Deloukas; Willem H. Ouwehand; Christian Gieger

doi:10.1038/ng.467

A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium

Nicole Soranzo^*, Tim D. Spector, Massimo Mangino, Brigitte Kühnel, Augusto Rendon, Alexander Teumer, Christina Willenborg, Benjamin Wright, Li Chen, Mingyao Li, Perttu Salo, Benjamin F. Voight, Philippa Burns, Roman A. Laskowski, Yali Xue, Stephan Menzel, David Altshuler, John R. Bradley, Suzannah Bumpstead, Mary Susan BurnettJoseph Devaney, Angela Döring, Roberto Elosua, Stephen E. Epstein, Wendy Erber, Mario Falchi, Stephen F. Garner, Mohammed J.R. Ghori, Alison H. Goodall, Rhian Gwilliam, Hakon H. Hakonarson, Alistair S. Hall, Naomi Hammond, Christian Hengstenberg, Thomas Illig, Inke R. König, Christopher W. Knouff, Ruth McPherson, Olle Melander, Vincent Mooser, Matthias Nauck, Markku S. Nieminen, Christopher J. O'Donnell, Leena Peltonen, Simon C. Potter, Holger Prokisch, Daniel J. Rader, Catherine M. Rice, Robert Roberts, Veikko Salomaa, Jennifer Sambrook, Stefan Schreiber, Heribert Schunkert, Stephen M. Schwartz, Jovana Serbanovic-Canic, Juha Sinisalo, David S. Siscovick, Klaus Stark, Ida Surakka, Jonathan Stephens, John R. Thompson, Uwe Völker, Henry Völzke, Nicholas A. Watkins, George A. Wells, H. Erich Wichmann, David A. Van Heel, Chris Tyler-Smith, Swee Lay Thein, Sekar Kathiresan, Markus Perola, Muredach P. Reilly, Alexandre F.R. Stewart, Jeanette Erdmann, Nilesh J. Samani, Christa Meisinger, Andreas Greinacher, Panos Deloukas, Willem H. Ouwehand, Christian Gieger

^*Corresponding author for this work

322 Citations (Scopus)

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.

Original language	English
Journal	Nature Genetics
Volume	41
Issue number	11
Pages (from-to)	1182-1190
Number of pages	9
ISSN	1061-4036
DOIs	https://doi.org/10.1038/ng.467
Publication status	Published - 01.11.2009

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Soranzo, N., Spector, T. D., Mangino, M., Kühnel, B., Rendon, A., Teumer, A., Willenborg, C., Wright, B., Chen, L., Li, M., Salo, P., Voight, B. F., Burns, P., Laskowski, R. A., Xue, Y., Menzel, S., Altshuler, D., Bradley, J. R., Bumpstead, S., ... Gieger, C. (2009). A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium. Nature Genetics, 41(11), 1182-1190. https://doi.org/10.1038/ng.467

@article{60df3352075141e2ac88820abe5484f7,

title = "A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium",

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.",

author = "Nicole Soranzo and Spector, {Tim D.} and Massimo Mangino and Brigitte K{\"u}hnel and Augusto Rendon and Alexander Teumer and Christina Willenborg and Benjamin Wright and Li Chen and Mingyao Li and Perttu Salo and Voight, {Benjamin F.} and Philippa Burns and Laskowski, {Roman A.} and Yali Xue and Stephan Menzel and David Altshuler and Bradley, {John R.} and Suzannah Bumpstead and Burnett, {Mary Susan} and Joseph Devaney and Angela D{\"o}ring and Roberto Elosua and Epstein, {Stephen E.} and Wendy Erber and Mario Falchi and Garner, {Stephen F.} and Ghori, {Mohammed J.R.} and Goodall, {Alison H.} and Rhian Gwilliam and Hakonarson, {Hakon H.} and Hall, {Alistair S.} and Naomi Hammond and Christian Hengstenberg and Thomas Illig and K{\"o}nig, {Inke R.} and Knouff, {Christopher W.} and Ruth McPherson and Olle Melander and Vincent Mooser and Matthias Nauck and Nieminen, {Markku S.} and O'Donnell, {Christopher J.} and Leena Peltonen and Potter, {Simon C.} and Holger Prokisch and Rader, {Daniel J.} and Rice, {Catherine M.} and Robert Roberts and Veikko Salomaa and Jennifer Sambrook and Stefan Schreiber and Heribert Schunkert and Schwartz, {Stephen M.} and Jovana Serbanovic-Canic and Juha Sinisalo and Siscovick, {David S.} and Klaus Stark and Ida Surakka and Jonathan Stephens and Thompson, {John R.} and Uwe V{\"o}lker and Henry V{\"o}lzke and Watkins, {Nicholas A.} and Wells, {George A.} and Wichmann, {H. Erich} and {Van Heel}, {David A.} and Chris Tyler-Smith and Thein, {Swee Lay} and Sekar Kathiresan and Markus Perola and Reilly, {Muredach P.} and Stewart, {Alexandre F.R.} and Jeanette Erdmann and Samani, {Nilesh J.} and Christa Meisinger and Andreas Greinacher and Panos Deloukas and Ouwehand, {Willem H.} and Christian Gieger",

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Soranzo, N, Spector, TD, Mangino, M, Kühnel, B, Rendon, A, Teumer, A, Willenborg, C, Wright, B, Chen, L, Li, M, Salo, P, Voight, BF, Burns, P, Laskowski, RA, Xue, Y, Menzel, S, Altshuler, D, Bradley, JR, Bumpstead, S, Burnett, MS, Devaney, J, Döring, A, Elosua, R, Epstein, SE, Erber, W, Falchi, M, Garner, SF, Ghori, MJR, Goodall, AH, Gwilliam, R, Hakonarson, HH, Hall, AS, Hammond, N, Hengstenberg, C, Illig, T, König, IR, Knouff, CW, McPherson, R, Melander, O, Mooser, V, Nauck, M, Nieminen, MS, O'Donnell, CJ, Peltonen, L, Potter, SC, Prokisch, H, Rader, DJ, Rice, CM, Roberts, R, Salomaa, V, Sambrook, J, Schreiber, S, Schunkert, H, Schwartz, SM, Serbanovic-Canic, J, Sinisalo, J, Siscovick, DS, Stark, K, Surakka, I, Stephens, J, Thompson, JR, Völker, U, Völzke, H, Watkins, NA, Wells, GA, Wichmann, HE, Van Heel, DA, Tyler-Smith, C, Thein, SL, Kathiresan, S, Perola, M, Reilly, MP, Stewart, AFR, Erdmann, J, Samani, NJ, Meisinger, C, Greinacher, A, Deloukas, P, Ouwehand, WH & Gieger, C 2009, 'A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium', Nature Genetics, vol. 41, no. 11, pp. 1182-1190. https://doi.org/10.1038/ng.467

TY - JOUR

T1 - A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium

AU - Soranzo, Nicole

AU - Spector, Tim D.

AU - Mangino, Massimo

AU - Kühnel, Brigitte

AU - Rendon, Augusto

AU - Teumer, Alexander

AU - Willenborg, Christina

AU - Wright, Benjamin

AU - Chen, Li

AU - Li, Mingyao

AU - Salo, Perttu

AU - Voight, Benjamin F.

AU - Burns, Philippa

AU - Laskowski, Roman A.

AU - Xue, Yali

AU - Menzel, Stephan

AU - Altshuler, David

AU - Bradley, John R.

AU - Bumpstead, Suzannah

AU - Burnett, Mary Susan

AU - Devaney, Joseph

AU - Döring, Angela

AU - Elosua, Roberto

AU - Epstein, Stephen E.

AU - Erber, Wendy

AU - Falchi, Mario

AU - Garner, Stephen F.

AU - Ghori, Mohammed J.R.

AU - Goodall, Alison H.

AU - Gwilliam, Rhian

AU - Hakonarson, Hakon H.

AU - Hall, Alistair S.

AU - Hammond, Naomi

AU - Hengstenberg, Christian

AU - Illig, Thomas

AU - König, Inke R.

AU - Knouff, Christopher W.

AU - McPherson, Ruth

AU - Melander, Olle

AU - Mooser, Vincent

AU - Nauck, Matthias

AU - Nieminen, Markku S.

AU - O'Donnell, Christopher J.

AU - Peltonen, Leena

AU - Potter, Simon C.

AU - Prokisch, Holger

AU - Rader, Daniel J.

AU - Rice, Catherine M.

AU - Roberts, Robert

AU - Salomaa, Veikko

AU - Sambrook, Jennifer

AU - Schreiber, Stefan

AU - Schunkert, Heribert

AU - Schwartz, Stephen M.

AU - Serbanovic-Canic, Jovana

AU - Sinisalo, Juha

AU - Siscovick, David S.

AU - Stark, Klaus

AU - Surakka, Ida

AU - Stephens, Jonathan

AU - Thompson, John R.

AU - Völker, Uwe

AU - Völzke, Henry

AU - Watkins, Nicholas A.

AU - Wells, George A.

AU - Wichmann, H. Erich

AU - Van Heel, David A.

AU - Tyler-Smith, Chris

AU - Thein, Swee Lay

AU - Kathiresan, Sekar

AU - Perola, Markus

AU - Reilly, Muredach P.

AU - Stewart, Alexandre F.R.

AU - Erdmann, Jeanette

AU - Samani, Nilesh J.

AU - Meisinger, Christa

AU - Greinacher, Andreas

AU - Deloukas, Panos

AU - Ouwehand, Willem H.

AU - Gieger, Christian

PY - 2009/11/1

Y1 - 2009/11/1

N2 - 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.

AB - 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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U2 - 10.1038/ng.467

DO - 10.1038/ng.467

M3 - Journal articles

C2 - 19820697

AN - SCOPUS:70350644759

SN - 1061-4036

VL - 41

SP - 1182

EP - 1190

JO - Nature Genetics

JF - Nature Genetics

IS - 11

ER -

A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium

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