PUBLICATION
New gene functions in megakaryopoiesis and platelet formation
- Authors
- 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., Khaw, K.T., 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.
- ID
- ZDB-PUB-160411-7
- Date
- 2011
- Source
- Nature 480: 201-8 (Journal)
- Registered Authors
- Stemple, Derek L.
- Keywords
- Genetics, Genomics, Disease
- MeSH Terms
-
- Animals
- Blood Platelets/cytology*
- Blood Platelets/metabolism
- Cell Size
- Drosophila Proteins/genetics
- Drosophila melanogaster/genetics
- Europe
- Gene Expression Profiling
- Gene Silencing
- Genome, Human/genetics
- Genome-Wide Association Study
- Hematopoiesis/genetics*
- Humans
- Megakaryocytes/cytology*
- Megakaryocytes/metabolism
- Platelet Count
- Protein Interaction Maps
- Transcription, Genetic/genetics
- Zebrafish/genetics
- Zebrafish Proteins/genetics
- PubMed
- 22139419 Full text @ Nature
Citation
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., Khaw, K.T., 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. (2011) New gene functions in megakaryopoiesis and platelet formation. Nature. 480:201-8.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping