New gene functions in megakaryopoiesis and platelet formation.

Gieger, C.; Radhakrishnan, A.; Cvejic, A.; Tang, W.; Porcu, E.; Pistis, G.; Serbanovic-Canic, J.; Elling, U.; Goodall, A.H.; Labrune, Y.; Lopez, L.M.; Mägi, R.; Meacham, S.; Okada, Y.; Pirastu, N.; Sorice, R.; Teumer, A.; Voss, K.; Zhang, W.; Ramirez-Solis, R.; Bis, J.C.; Ellinghaus, D.; Gögele, M.; Hottenga, J.J.; Langenberg, C.; Kovacs, P.; O'Reilly, P.F.; Shin, S.Y.; Esko, T.; Hartiala, J.; Kanoni, S.; Murgia, F.; Parsa, A.; Stephens, J.; van der Harst, P.; Ellen van der Schoot, C.; Allayee, H.; Attwood, A.; Balkau, B.; Bastardot, F.; Basu, S.; Baumeister, S.E.; Biino, G.; Bomba, L.; Bonnefond, A.; Cambien, F.; Chambers, J.C.; Cucca, F.; D'Adamo, P.; Davies, G.; de Boer, R.A.; de Geus, E.J.; Döring, A.; Elliott, P.; Erdmann, J.; Evans, D.M.; Falchi, M.; Feng, W.; Folsom, A.R.; Frazer, I.H.; Gibson, Q.D.; Glazer, N.L.; Hammond, C.; Hartikainen, A.L.; Heckbert, S.R.; Hengstenberg, C.; Hersch, M.; Illig, T.; Loos, R.J.; Jolley, J.; Tee Khaw, K.; Kühnel, B.; Kyrtsonis, M.C.; Lagou, V.; Lloyd-Jones, H.; Lumley, T.; Mangino, M.; Maschio, A.; Mateo Leach, I.; McKnight, B.; Memari, Y.; Mitchell, B.D.; Montgomery, G.W.; Nakamura, Y.; Nauck, M.; Navis, G.; Nöthlings, U.; Nolte, I.M.; Porteous, D.J.; Pouta, A.; Pramstaller, P.P.; Pullat, J.; Ring, S.M.; Rotter, J.I.; Ruggiero, D.; Ruokonen, A.; Sala, C.; Samani, N.J.; Sambrook, J.; Schlessinger, D.; Schreiber, S.; Schunkert, H.; Scott, J.; Smith, N.L.; Snieder, H.; Starr, J.M.; Stumvoll, M.; Takahashi, A.; Tang, W.H.; Taylor, K.; Tenesa, A.; Lay Thein, S.; Tönjes, A.; Uda, M.; Ulivi, S.; van Veldhuisen, D.J.; Visscher, P.M.; Völker, U.; Wichmann, H.E.; Wiggins, K.L.; Willemsen, G.; Yang, T.P.; Hua Zhao, J.; Zitting, P.; Bradley, J.R.; Dedoussis, G.V.; Gasparini, P.; Hazen, S.L.; Metspalu, A.; Pirastu, M.; Shuldiner, A.R.; Joost van Pelt, L.; Zwaginga, J.J.; Boomsma, D.I.; Deary, I.J.; Franke, A.; Froguel, P.; Ganesh, S.K.; Jarvelin, M.R.; Martin, N.G.; Meisinger, C.; Psaty, B.M.; Spector, T.D.; Wareham, N.J.; Akkerman, J.W.; Ciullo, M.; Deloukas, P.; Greinacher, A.; Jupe, S.; Kamatani, N.; Khadake, J.; Kooner, J.S.; Penninger, J.; Prokopenko, I.; Stemple, D.; Toniolo, D.; Wernisch, L.; Sanna, S.; Hicks, A.A.; Rendon, A.; Ferreira, M.A.; Ouwehand, W.H.; Soranzo, N.

doi:10.1038/nature10659

New gene functions in megakaryopoiesis and platelet formation.

Details

Download: 22139419_Postprint.pdf (1207.82 [Ko])
State: Public
Version: author

Serval ID

serval:BIB_5793840A79A2

Type

Article: article from journal or magazin.

Collection

Publications

Institution

UNIL/CHUV

Title

New gene functions in megakaryopoiesis and platelet formation.

Journal

Nature

Author(s)

Gieger C., Radhakrishnan A., Cvejic A., Tang W., Porcu E., Pistis G., Serbanovic-Canic J., Elling U., Goodall A.H., Labrune Y., Lopez L.M., Mägi R., Meacham S., Okada Y., Pirastu N., Sorice R., Teumer A., Voss K., Zhang W., Ramirez-Solis R., Bis J.C., Ellinghaus D., Gögele M., Hottenga J.J., Langenberg C., Kovacs P., O'Reilly P.F., Shin S.Y., Esko T., Hartiala J., Kanoni S., Murgia F., Parsa A., Stephens J., van der Harst P., Ellen van der Schoot C., Allayee H., Attwood A., Balkau B., Bastardot F., Basu S., Baumeister S.E., Biino G., Bomba L., Bonnefond A., Cambien F., Chambers J.C., Cucca F., D'Adamo P., Davies G., de Boer R.A., de Geus E.J., Döring A., Elliott P., Erdmann J., Evans D.M., Falchi M., Feng W., Folsom A.R., Frazer I.H., Gibson Q.D., Glazer N.L., Hammond C., Hartikainen A.L., Heckbert S.R., Hengstenberg C., Hersch M., Illig T., Loos R.J., Jolley J., Tee Khaw K., Kühnel B., Kyrtsonis M.C., Lagou V., Lloyd-Jones H., Lumley T., Mangino M., Maschio A., Mateo Leach I., McKnight B., Memari Y., Mitchell B.D., Montgomery G.W., Nakamura Y., Nauck M., Navis G., Nöthlings U., Nolte I.M., Porteous D.J., Pouta A., Pramstaller P.P., Pullat J., Ring S.M., Rotter J.I., Ruggiero D., Ruokonen A., Sala C., Samani N.J., Sambrook J., Schlessinger D., Schreiber S., Schunkert H., Scott J., Smith N.L., Snieder H., Starr J.M., Stumvoll M., Takahashi A., Tang W.H., Taylor K., Tenesa A., Lay Thein S., Tönjes A., Uda M., Ulivi S., van Veldhuisen D.J., Visscher P.M., Völker U., Wichmann H.E., Wiggins K.L., Willemsen G., Yang T.P., Hua Zhao J., Zitting P., Bradley J.R., Dedoussis G.V., Gasparini P., Hazen S.L., Metspalu A., Pirastu M., Shuldiner A.R., Joost van Pelt L., Zwaginga J.J., Boomsma D.I., Deary I.J., Franke A., Froguel P., Ganesh S.K., Jarvelin M.R., Martin N.G., Meisinger C., Psaty B.M., Spector T.D., Wareham N.J., Akkerman J.W., Ciullo M., Deloukas P., Greinacher A., Jupe S., Kamatani N., Khadake J., Kooner J.S., Penninger J., Prokopenko I., Stemple D., Toniolo D., Wernisch L., Sanna S., Hicks A.A., Rendon A., Ferreira M.A., Ouwehand W.H., Soranzo N.

ISSN

1476-4687 (Electronic)

ISSN-L

0028-0836

Publication state

Published

Issued date

2011

Volume

480

Number

7376

Pages

201-208

Language

english

Notes

Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov'tPublication Status: epublish

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.

URN

urn:nbn:ch:serval-BIB_5793840A79A23

OAI-PMH

oai:serval.unil.ch:BIB_5793840A79A2

DOI

10.1038/nature10659

Pubmed

22139419

Web of science

000297744200043

Open Access

Yes