New gene functions in megakaryopoiesis and platelet formation.

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Version: author
Serval ID
serval:BIB_5793840A79A2
Type
Article: article from journal or magazin.
Collection
Publications
Institution
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.
Pubmed
Web of science
Open Access
Yes
Create date
22/12/2011 11:32
Last modification date
20/08/2019 15:11
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