New gene functions in megakaryopoiesis and platelet formation

C. Gieger; A. Radhakrishnan; A. Cvejic; W. Tang; E. Porcu; G. Pistis; J. Serbanovic-Canic; U. Elling; A.H. Goodall; Y. Labrune; J.J. Hottenga; E.J.C. de Geus; GW Montgomery; P.M. Visscher; G. Willemsen; D.I. Boomsma; N.G. Martin; T.D. Spector; I. Prokopenko; D. Stemple; L. Toniolo; L. Wernisch; S. Sanna; A.A. Hicks; A. Rendon; M.A. Ferreira; W.H. Ouwehand; N. Soranzo

doi:10.1038/nature10659

New gene functions in megakaryopoiesis and platelet formation

C. Gieger, A. Radhakrishnan, A. Cvejic, W. Tang, E. Porcu, G. Pistis, J. Serbanovic-Canic, U. Elling, A.H. Goodall, Y. Labrune, J.J. Hottenga, E.J.C. de Geus, GW Montgomery, P.M. Visscher, G. Willemsen, D.I. Boomsma, N.G. Martin, T.D. Spector, I. Prokopenko, D. StempleL. Toniolo, L. Wernisch, S. Sanna, A.A. Hicks, A. Rendon, M.A. Ferreira, W.H. Ouwehand, N. Soranzo

Biological Psychology

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

Platelets are the second most abundant cell type in blood and are essential for maintaining haemostasis. Their count and volume are tightly controlled within narrow physiological ranges, but there is only limited understanding of the molecular processes controlling both traits. Here we carried out a high-powered meta-analysis of genome-wide association studies (GWAS) in up to 66,867 individuals of European ancestry, followed by extensive biological and functional assessment. We identified 68 genomic loci reliably associated with platelet count and volume mapping to established and putative novel regulators of megakaryopoiesis and platelet formation. These genes show megakaryocyte-specific gene expression patterns and extensive network connectivity. Using gene silencing in Danio rerio and Drosophila melanogaster, we identified 11 of the genes as novel regulators of blood cell formation. Taken together, our findings advance understanding of novel gene functions controlling fate-determining events during megakaryopoiesis and platelet formation, providing a new example of successful translation of GWAS to function. © 2011 Macmillan Publishers Limited. All rights reserved.

Original language	English
Pages (from-to)	201-208
Journal	Nature
Volume	480
Issue number	7376
DOIs	https://doi.org/10.1038/nature10659
Publication status	Published - 2011

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Gieger, C., Radhakrishnan, A., Cvejic, A., Tang, W., Porcu, E., Pistis, G., Serbanovic-Canic, J., Elling, U., Goodall, A. H., Labrune, Y., Hottenga, J. J., de Geus, E. J. C., Montgomery, GW., Visscher, P. M., Willemsen, G., Boomsma, D. I., Martin, N. G., Spector, T. D., Prokopenko, I., ... Soranzo, N. (2011). New gene functions in megakaryopoiesis and platelet formation. Nature, 480(7376), 201-208. https://doi.org/10.1038/nature10659

@article{896a73817c84456dba39d9461923c940,

title = "New gene functions in megakaryopoiesis and platelet formation",

abstract = "Platelets are the second most abundant cell type in blood and are essential for maintaining haemostasis. Their count and volume are tightly controlled within narrow physiological ranges, but there is only limited understanding of the molecular processes controlling both traits. Here we carried out a high-powered meta-analysis of genome-wide association studies (GWAS) in up to 66,867 individuals of European ancestry, followed by extensive biological and functional assessment. We identified 68 genomic loci reliably associated with platelet count and volume mapping to established and putative novel regulators of megakaryopoiesis and platelet formation. These genes show megakaryocyte-specific gene expression patterns and extensive network connectivity. Using gene silencing in Danio rerio and Drosophila melanogaster, we identified 11 of the genes as novel regulators of blood cell formation. Taken together, our findings advance understanding of novel gene functions controlling fate-determining events during megakaryopoiesis and platelet formation, providing a new example of successful translation of GWAS to function. {\textcopyright} 2011 Macmillan Publishers Limited. All rights reserved.",

author = "C. Gieger and A. Radhakrishnan and A. Cvejic and W. Tang and E. Porcu and G. Pistis and J. Serbanovic-Canic and U. Elling and A.H. Goodall and Y. Labrune and J.J. Hottenga and {de Geus}, E.J.C. and GW Montgomery and P.M. Visscher and G. Willemsen and D.I. Boomsma and N.G. Martin and T.D. Spector and I. Prokopenko and D. Stemple and L. Toniolo and L. Wernisch and S. Sanna and A.A. Hicks and A. Rendon and M.A. Ferreira and W.H. Ouwehand and N. Soranzo",

year = "2011",

doi = "10.1038/nature10659",

language = "English",

volume = "480",

pages = "201--208",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Publishing Group",

number = "7376",

}

Gieger, C, Radhakrishnan, A, Cvejic, A, Tang, W, Porcu, E, Pistis, G, Serbanovic-Canic, J, Elling, U, Goodall, AH, Labrune, Y, Hottenga, JJ , de Geus, EJC, Montgomery, GW, Visscher, PM, Willemsen, G, Boomsma, DI, Martin, NG, Spector, TD, Prokopenko, I, Stemple, D, Toniolo, L, Wernisch, L, Sanna, S, Hicks, AA, Rendon, A, Ferreira, MA, Ouwehand, WH & Soranzo, N 2011, 'New gene functions in megakaryopoiesis and platelet formation', Nature, vol. 480, no. 7376, pp. 201-208. https://doi.org/10.1038/nature10659

TY - JOUR

T1 - New gene functions in megakaryopoiesis and platelet formation

AU - Gieger, C.

AU - Radhakrishnan, A.

AU - Cvejic, A.

AU - Tang, W.

AU - Porcu, E.

AU - Pistis, G.

AU - Serbanovic-Canic, J.

AU - Elling, U.

AU - Goodall, A.H.

AU - Labrune, Y.

AU - Hottenga, J.J.

AU - de Geus, E.J.C.

AU - Montgomery, GW

AU - Visscher, P.M.

AU - Willemsen, G.

AU - Boomsma, D.I.

AU - Martin, N.G.

AU - Spector, T.D.

AU - Prokopenko, I.

AU - Stemple, D.

AU - Toniolo, L.

AU - Wernisch, L.

AU - Sanna, S.

AU - Hicks, A.A.

AU - Rendon, A.

AU - Ferreira, M.A.

AU - Ouwehand, W.H.

AU - Soranzo, N.

PY - 2011

Y1 - 2011

N2 - Platelets are the second most abundant cell type in blood and are essential for maintaining haemostasis. Their count and volume are tightly controlled within narrow physiological ranges, but there is only limited understanding of the molecular processes controlling both traits. Here we carried out a high-powered meta-analysis of genome-wide association studies (GWAS) in up to 66,867 individuals of European ancestry, followed by extensive biological and functional assessment. We identified 68 genomic loci reliably associated with platelet count and volume mapping to established and putative novel regulators of megakaryopoiesis and platelet formation. These genes show megakaryocyte-specific gene expression patterns and extensive network connectivity. Using gene silencing in Danio rerio and Drosophila melanogaster, we identified 11 of the genes as novel regulators of blood cell formation. Taken together, our findings advance understanding of novel gene functions controlling fate-determining events during megakaryopoiesis and platelet formation, providing a new example of successful translation of GWAS to function. © 2011 Macmillan Publishers Limited. All rights reserved.

AB - Platelets are the second most abundant cell type in blood and are essential for maintaining haemostasis. Their count and volume are tightly controlled within narrow physiological ranges, but there is only limited understanding of the molecular processes controlling both traits. Here we carried out a high-powered meta-analysis of genome-wide association studies (GWAS) in up to 66,867 individuals of European ancestry, followed by extensive biological and functional assessment. We identified 68 genomic loci reliably associated with platelet count and volume mapping to established and putative novel regulators of megakaryopoiesis and platelet formation. These genes show megakaryocyte-specific gene expression patterns and extensive network connectivity. Using gene silencing in Danio rerio and Drosophila melanogaster, we identified 11 of the genes as novel regulators of blood cell formation. Taken together, our findings advance understanding of novel gene functions controlling fate-determining events during megakaryopoiesis and platelet formation, providing a new example of successful translation of GWAS to function. © 2011 Macmillan Publishers Limited. All rights reserved.

U2 - 10.1038/nature10659

DO - 10.1038/nature10659

M3 - Article

SN - 0028-0836

VL - 480

SP - 201

EP - 208

JO - Nature

JF - Nature

IS - 7376

ER -

New gene functions in megakaryopoiesis and platelet formation

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