Gieger, Christian and Radhakrishnan, Aparna and Cvejic, Ana and Tang, Weihong and Porcu, Eleonora and Pistis, Giorgio and Serbanovic-Canic, Jovana and Elling, Ulrich and Goodall, Alison H. and Labrune, Yann and Lopez, Lorna M. and Mägi, Reedik and Meacham, Stuart and Okada, Yukinori and Pirastu, Nicola and Sorice, Rossella and Teumer, Alexander and Voss, Katrin and Zhang, Weihua and Ramirez-Solis, Ramiro and Bis, Joshua C. and Ellinghaus, David and Gögele, Martin and Hottenga, Jouke-Jan and Langenberg, Claudia and Kovacs, Peter and O’Reilly, Paul F. and Shin, So-Youn and Esko, Tõnu and Hartiala, Jaana and Kanoni, Stavroula and Murgia, Federico and Parsa, Afshin and Stephens, Jonathan and van der Harst, Pim and Ellen van der Schoot, C. and Allayee, Hooman and Attwood, Antony and Balkau, Beverley and Bastardot, François and Basu, Saonli and Baumeister, Sebastian E. and Biino, Ginevra and Bomba, Lorenzo and Bonnefond, Amélie and Cambien, François and Chambers, John C. and Cucca, Francesco and D’Adamo, Pio and Davies, Gail and de Boer, Rudolf A. and de Geus, Eco J. C. and Döring, Angela and Elliott, Paul and Erdmann, Jeanette and Evans, David M. and Falchi, Mario and Feng, Wei and Folsom, Aaron R. and Frazer, Ian H. and Gibson, Quince D. and Glazer, Nicole L. and Hammond, Chris and Hartikainen, Anna-Liisa and Heckbert, Susan R. and Hengstenberg, Christian and Hersch, Micha and Illig, Thomas and Loos, Ruth J. F. and Jolley, Jennifer and Khaw, Kay-Tee and Kühnel, Brigitte and Kyrtsonis, Marie-Christine and Lagou, Vasiliki and Lloyd-Jones, Heather and Lumley, Thomas and Mangino, Massimo and Maschio, Andrea and Mateo Leach, Irene and McKnight, Barbara and Memari, Yasin and Mitchell, Braxton D. and Montgomery, Grant W. and Nakamura, Yusuke and Nauck, Matthias and Navis, Gerjan and Nöthlings, Ute and Nolte, Ilja M. and Porteous, David J. and Pouta, Anneli and Pramstaller, Peter P. and Pullat, Janne and Ring, Susan M. and Rotter, Jerome I. and Ruggiero, Daniela and Ruokonen, Aimo and Sala, Cinzia and Samani, Nilesh J. and Sambrook, Jennifer and Schlessinger, David and Schreiber, Stefan and Schunkert, Heribert and Scott, James and Smith, Nicholas L. and Snieder, Harold and Starr, John M. and Stumvoll, Michael and Takahashi, Atsushi and Wilson Tang, W. H. and Taylor, Kent and Tenesa, Albert and Lay Thein, Swee and Tönjes, Anke and Uda, Manuela and Ulivi, Sheila and van Veldhuisen, Dirk J. and Visscher, Peter M. and Völker, Uwe and Wichmann, H.-Erich and Wiggins, Kerri L. and Willemsen, Gonneke and Yang, Tsun-Po and Hua Zhao, Jing and Zitting, Paavo and Bradley, John R. and Dedoussis, George V. and Gasparini, Paolo and Hazen, Stanley L. and Metspalu, Andres and Pirastu, Mario and Shuldiner, Alan R. and Joost van Pelt, L. and Zwaginga, Jaap-Jan and Boomsma, Dorret I. and Deary, Ian J. and Franke, Andre and Froguel, Philippe and Ganesh, Santhi K. and Jarvelin, Marjo-Riitta and Martin, Nicholas G. and Meisinger, Christa and Psaty, Bruce M. and Spector, Timothy D. and Wareham, Nicholas J. and Akkerman, Jan-Willem N. and Ciullo, Marina and Deloukas, Panos and Greinacher, Andreas and Jupe, Steve and Kamatani, Naoyuki and Khadake, Jyoti and Kooner, Jaspal S. and Penninger, Josef and Prokopenko, Inga and Stemple, Derek and Toniolo, Daniela and Wernisch, Lorenz and Sanna, Serena and Hicks, Andrew A. and Rendon, Augusto and Ferreira, Manuel A. and Ouwehand, Willem H. and Soranzo, Nicole (2011) New gene functions in megakaryopoiesis and platelet formation. Nature, 480 (7376). pp. 201-208. ISSN 0028-0836

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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.

Item Type:	Article
Keywords:	New gene; functions; megakaryopoiesis; platelet formation;
Academic Unit:	Faculty of Science and Engineering > Biology Faculty of Science and Engineering > Research Institutes > Human Health Institute
Item ID:	17401
Identification Number:	https://doi.org/10.1038/nature10659
Depositing User:	Lorna Lopez
Date Deposited:	10 Jul 2023 16:12
Journal or Publication Title:	Nature
Publisher:	Nature Research
Refereed:	Yes
URI:	Publisher
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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