Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 201-8 |
| Number of pages | 8 |
| Journal | Nature |
| Volume | 480 |
| Issue number | 7376 |
| DOIs | |
| Publication status | Published - 8 Dec 2011 |
Keywords
- Animals
- Zebrafish Proteins
- Cell Size
- Genome, Human
- Protein Interaction Maps
- Gene Silencing
- Humans
- Transcription, Genetic
- Europe
- Hematopoiesis
- Zebrafish
- Genome-Wide Association Study
- Gene Expression Profiling
- Blood Platelets
- Drosophila melanogaster
- Drosophila Proteins
- Megakaryocytes
- Platelet Count
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New gene functions in megakaryopoiesis and platelet formation. / Gieger, Christian; Radhakrishnan, Aparna; Cvejic, Ana; Tang, Weihong; Porcu, Eleonora; Pistis, Giorgio; Serbanovic-Canic, Jovana; Elling, Ulrich; Goodall, Alison H; Labrune, Yann; Lopez, Lorna M; Mägi, Reedik; Meacham, Stuart; Okada, Yukinori; Pirastu, Nicola; Sorice, Rossella; Teumer, Alexander; Voss, Katrin; Zhang, Weihua; Ramirez-Solis, Ramiro; Bis, Joshua C; Ellinghaus, David; Gögele, Martin; Hottenga, Jouke-Jan; Langenberg, Claudia; Kovacs, Peter; O'Reilly, Paul F; Shin, So-Youn; Esko, Tõnu; Hartiala, Jaana; Kanoni, Stavroula; Murgia, Federico; Parsa, Afshin; Stephens, Jonathan; van der Harst, Pim; Ellen van der Schoot, C; Allayee, Hooman; Attwood, Antony; Balkau, Beverley; Bastardot, François; Basu, Saonli; Baumeister, Sebastian E; Biino, Ginevra; Bomba, Lorenzo; Bonnefond, Amélie; Cambien, François; Chambers, John C; Cucca, Francesco; D'Adamo, Pio; Davies, Gail; de Boer, Rudolf A; de Geus, Eco J C; Döring, Angela; Elliott, Paul; Erdmann, Jeanette; Evans, David M; Falchi, Mario; Feng, Wei; Folsom, Aaron R; Frazer, Ian H; Gibson, Quince D; Glazer, Nicole L; Hammond, Chris; Hartikainen, Anna-Liisa; Heckbert, Susan R; Hengstenberg, Christian; Hersch, Micha; Illig, Thomas; Loos, Ruth J F; Jolley, Jennifer; Khaw, Kay Tee; Kühnel, Brigitte; Kyrtsonis, Marie-Christine; Lagou, Vasiliki; Lloyd-Jones, Heather; Lumley, Thomas; Mangino, Massimo; Maschio, Andrea; Mateo Leach, Irene; McKnight, Barbara; Memari, Yasin; Mitchell, Braxton D; Montgomery, Grant W; Nakamura, Yusuke; Nauck, Matthias; Navis, Gerjan; Nöthlings, Ute; Nolte, Ilja M; Porteous, David J; Pouta, Anneli; Pramstaller, Peter P; Pullat, Janne; Ring, Susan M; Rotter, Jerome I; Ruggiero, Daniela; Ruokonen, Aimo; Sala, Cinzia; Samani, Nilesh J; Sambrook, Jennifer; Schlessinger, David; Schreiber, Stefan; Schunkert, Heribert; Scott, James; Smith, Nicholas L; Snieder, Harold; Starr, John M; Stumvoll, Michael; Takahashi, Atsushi; Tang, W H Wilson; Taylor, Kent; Tenesa, Albert; Lay Thein, Swee; Tönjes, Anke; Uda, Manuela; Ulivi, Sheila; van Veldhuisen, Dirk J; Visscher, Peter M; Völker, Uwe; Wichmann, H-Erich; Wiggins, Kerri L; Willemsen, Gonneke; Yang, Tsun-Po; Hua Zhao, Jing; Zitting, Paavo; Bradley, John R; Dedoussis, George V; Gasparini, Paolo; Hazen, Stanley L; Metspalu, Andres; Pirastu, Mario; Shuldiner, Alan R; Joost van Pelt, L; Zwaginga, Jaap-Jan; Boomsma, Dorret I; Deary, Ian J; Franke, Andre; Froguel, Philippe; Ganesh, Santhi K; Jarvelin, Marjo-Riitta; Martin, Nicholas G; Meisinger, Christa; Psaty, Bruce M; Spector, Timothy D; Wareham, Nicholas J; Akkerman, Jan-Willem N; Ciullo, Marina; Deloukas, Panos; Greinacher, Andreas; Jupe, Steve; Kamatani, Naoyuki; Khadake, Jyoti; Kooner, Jaspal S; Penninger, Josef; Prokopenko, Inga; Stemple, Derek; Toniolo, Daniela; Wernisch, Lorenz; Sanna, Serena; Hicks, Andrew A; Rendon, Augusto; Ferreira, Manuel A; Ouwehand, Willem H; Soranzo, Nicole.
In: Nature, Vol. 480, No. 7376, 08.12.2011, p. 201-8.Research output: Contribution to journal › Article (Academic Journal) › peer-review
TY - JOUR
T1 - New gene functions in megakaryopoiesis and platelet formation
AU - Gieger, Christian
AU - Radhakrishnan, Aparna
AU - Cvejic, Ana
AU - Tang, Weihong
AU - Porcu, Eleonora
AU - Pistis, Giorgio
AU - Serbanovic-Canic, Jovana
AU - Elling, Ulrich
AU - Goodall, Alison H
AU - Labrune, Yann
AU - Lopez, Lorna M
AU - Mägi, Reedik
AU - Meacham, Stuart
AU - Okada, Yukinori
AU - Pirastu, Nicola
AU - Sorice, Rossella
AU - Teumer, Alexander
AU - Voss, Katrin
AU - Zhang, Weihua
AU - Ramirez-Solis, Ramiro
AU - Bis, Joshua C
AU - Ellinghaus, David
AU - Gögele, Martin
AU - Hottenga, Jouke-Jan
AU - Langenberg, Claudia
AU - Kovacs, Peter
AU - O'Reilly, Paul F
AU - Shin, So-Youn
AU - Esko, Tõnu
AU - Hartiala, Jaana
AU - Kanoni, Stavroula
AU - Murgia, Federico
AU - Parsa, Afshin
AU - Stephens, Jonathan
AU - van der Harst, Pim
AU - Ellen van der Schoot, C
AU - Allayee, Hooman
AU - Attwood, Antony
AU - Balkau, Beverley
AU - Bastardot, François
AU - Basu, Saonli
AU - Baumeister, Sebastian E
AU - Biino, Ginevra
AU - Bomba, Lorenzo
AU - Bonnefond, Amélie
AU - Cambien, François
AU - Chambers, John C
AU - Cucca, Francesco
AU - D'Adamo, Pio
AU - Davies, Gail
AU - de Boer, Rudolf A
AU - de Geus, Eco J C
AU - Döring, Angela
AU - Elliott, Paul
AU - Erdmann, Jeanette
AU - Evans, David M
AU - Falchi, Mario
AU - Feng, Wei
AU - Folsom, Aaron R
AU - Frazer, Ian H
AU - Gibson, Quince D
AU - Glazer, Nicole L
AU - Hammond, Chris
AU - Hartikainen, Anna-Liisa
AU - Heckbert, Susan R
AU - Hengstenberg, Christian
AU - Hersch, Micha
AU - Illig, Thomas
AU - Loos, Ruth J F
AU - Jolley, Jennifer
AU - Khaw, Kay Tee
AU - Kühnel, Brigitte
AU - Kyrtsonis, Marie-Christine
AU - Lagou, Vasiliki
AU - Lloyd-Jones, Heather
AU - Lumley, Thomas
AU - Mangino, Massimo
AU - Maschio, Andrea
AU - Mateo Leach, Irene
AU - McKnight, Barbara
AU - Memari, Yasin
AU - Mitchell, Braxton D
AU - Montgomery, Grant W
AU - Nakamura, Yusuke
AU - Nauck, Matthias
AU - Navis, Gerjan
AU - Nöthlings, Ute
AU - Nolte, Ilja M
AU - Porteous, David J
AU - Pouta, Anneli
AU - Pramstaller, Peter P
AU - Pullat, Janne
AU - Ring, Susan M
AU - Rotter, Jerome I
AU - Ruggiero, Daniela
AU - Ruokonen, Aimo
AU - Sala, Cinzia
AU - Samani, Nilesh J
AU - Sambrook, Jennifer
AU - Schlessinger, David
AU - Schreiber, Stefan
AU - Schunkert, Heribert
AU - Scott, James
AU - Smith, Nicholas L
AU - Snieder, Harold
AU - Starr, John M
AU - Stumvoll, Michael
AU - Takahashi, Atsushi
AU - Tang, W H Wilson
AU - Taylor, Kent
AU - Tenesa, Albert
AU - Lay Thein, Swee
AU - Tönjes, Anke
AU - Uda, Manuela
AU - Ulivi, Sheila
AU - van Veldhuisen, Dirk J
AU - Visscher, Peter M
AU - Völker, Uwe
AU - Wichmann, H-Erich
AU - Wiggins, Kerri L
AU - Willemsen, Gonneke
AU - Yang, Tsun-Po
AU - Hua Zhao, Jing
AU - Zitting, Paavo
AU - Bradley, John R
AU - Dedoussis, George V
AU - Gasparini, Paolo
AU - Hazen, Stanley L
AU - Metspalu, Andres
AU - Pirastu, Mario
AU - Shuldiner, Alan R
AU - Joost van Pelt, L
AU - Zwaginga, Jaap-Jan
AU - Boomsma, Dorret I
AU - Deary, Ian J
AU - Franke, Andre
AU - Froguel, Philippe
AU - Ganesh, Santhi K
AU - Jarvelin, Marjo-Riitta
AU - Martin, Nicholas G
AU - Meisinger, Christa
AU - Psaty, Bruce M
AU - Spector, Timothy D
AU - Wareham, Nicholas J
AU - Akkerman, Jan-Willem N
AU - Ciullo, Marina
AU - Deloukas, Panos
AU - Greinacher, Andreas
AU - Jupe, Steve
AU - Kamatani, Naoyuki
AU - Khadake, Jyoti
AU - Kooner, Jaspal S
AU - Penninger, Josef
AU - Prokopenko, Inga
AU - Stemple, Derek
AU - Toniolo, Daniela
AU - Wernisch, Lorenz
AU - Sanna, Serena
AU - Hicks, Andrew A
AU - Rendon, Augusto
AU - Ferreira, Manuel A
AU - Ouwehand, Willem H
AU - Soranzo, Nicole
PY - 2011/12/8
Y1 - 2011/12/8
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.
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.
KW - Animals
KW - Zebrafish Proteins
KW - Cell Size
KW - Genome, Human
KW - Protein Interaction Maps
KW - Gene Silencing
KW - Humans
KW - Transcription, Genetic
KW - Europe
KW - Hematopoiesis
KW - Zebrafish
KW - Genome-Wide Association Study
KW - Gene Expression Profiling
KW - Blood Platelets
KW - Drosophila melanogaster
KW - Drosophila Proteins
KW - Megakaryocytes
KW - Platelet Count
U2 - 10.1038/nature10659
DO - 10.1038/nature10659
M3 - Article (Academic Journal)
C2 - 22139419
VL - 480
SP - 201
EP - 208
JO - Nature
JF - Nature
SN - 0028-0836
IS - 7376
ER -