Platelet-Related Variants Identified by Exomechip Meta-analysis in 157,293 Individuals
| Autor: | Anne-Claire Vergnaud, Nauder Faraday, Tim Kacprowski, Lisa R. Yanek, Oscar H. Franco, Yongmei Liu, Andreas Greinacher, Gina M. Peloso, Cristen J. Willer, Leslie A. Lange, Eric S. Torstenson, Reedik Mägi, Jeanette Erdmann, Ethan M. Lange, Deborah A. Nickerson, Henry Völzke, David R. Crosslin, Gunnar Engström, Albert V. Smith, André G. Uitterlinden, Salman M. Tajuddin, W. David Hill, Diane M. Becker, Paul Elliot, Caterina Vacchi-Suzzi, Linda M. Polfus, Traci M. Bartz, Nathalie Chami, Abbas Dehghan, Mike A. Nalls, John D. Eicher, Leo-Pekka Lyytikäinen, Evelin Mihailov, Uwe Völker, Caroline Hayward, Ioanna Tzoulaki, Myriam Fornage, Marju Orho-Melander, Mary Cushman, Lars Wallentin, Terho Lehtimäki, Ayush Giri, Laura M. Raffield, Lewis C. Becker, Yingchang Lu, Emma Raitoharju, Sekar Kathiresan, Simon de Denus, Ruth J. F. Loos, James S. Floyd, Dawn M. Waterworth, James G. Wilson, Nathan Pankratz, Lenore J. Launer, Andrew D. Johnson, Andrew J. Slater, Jean-Claude Tardif, Raha Pazoki, Evangelos Evangelou, Kenneth Rice, Harvey D. White, Marie-Pierre Dubé, Frank J. A. van Rooij, Akihiro Nomura, Tamara B. Harris, Vilmundur Gudnason, Gonçalo R. Abecasis, Alan B. Zonderman, Guillaume Lettre, Todd L. Edwards, Amber A. Burt, Ani Manichaikul, Heribert Schunkert, Ming-Huei Chen, Ian J. Deary, Michelle L. O'Donoghue, Jennifer A. Brody, Russell P. Tracy, Tõnu Esko, Mika Kähönen, Panos Deloukas, Eric Boerwinkle, Rasika A. Mathias, Dajiang J. Liu, Jin Li, Santhi K. Ganesh, David C. Liewald, Paul L. Auer, Digna R. Velez Edwards, Erwin P. Bottinger, Nina Mononen, Claudia Schurmann, Michele K. Evans, John M. Starr, Thomas Thiele, Jussi Hernesniemi, Jerome I. Rotter, Rakale C. Quarells, He Gao, Kjell Nikus, Stephen S. Rich, Heather M. Highland, Bruce M. Psaty, Ursula M. Schick, Andres Metspalu, Melissa A. Richard, Neil A. Zakai, Olle Melander, John D. Rioux, Olli T. Raitakari, Alexander P. Reiner, Joel N. Hirschhorn, Nilesh J. Samani |
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| Přispěvatelé: | Epidemiology, Internal Medicine, Home Office, National Institute for Health Research, Medical Research Council (MRC) |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Blood Platelets Male CARDIoGRAM Exome Consortium Genome-wide association study 030204 cardiovascular system & hematology Biology Myocardial Infarction Genetics Consortium Article 03 medical and health sciences 0302 clinical medicine Genetics Humans Platelet Exome Genetics(clinical) Mean platelet volume Allele frequency Genotyping Genetics (clinical) Genetics & Heredity Platelet Count ta1184 Genetic Variation Global Lipids Genetics Consortium 11 Medical And Health Sciences 06 Biological Sciences FCER1A Genetic architecture 030104 developmental biology Hemostasis Immunology Female Mean Platelet Volume Genome-Wide Association Study |
| Zdroj: | American Journal of Human Genetics, 99(1), 40-55. Cell Press Eicher, J D, Chami, N, Kacprowski, T, Nomura, A, Chen, M-H, Yanek, L R, Tajuddin, S M, Schick, U M, Slater, A J, Pankratz, N, Polfus, L, Schurmann, C, Giri, A, Brody, J A, Lange, L A, Manichaikul, A, Hill, W D, Pazoki, R, Elliot, P, Evangelou, E, Tzoulaki, I, Gao, H, Vergnaud, A-C, Mathias, R A, Becker, D M, Becker, L C, Burt, A, Crosslin, D R, Lyytikäinen, L-P, Nikus, K, Hernesniemi, J, Kähönen, M, Raitoharju, E, Mononen, N, Raitakari, O T, Lehtimäki, T, Cushman, M, Zakai, N A, Nickerson, D A, Raffield, L M, Quarells, R, Willer, C J, Peloso, G M, Abecasis, G R, Liu, D J, Deloukas, P, Starr, J M, Liewald, D C M & Hayward, C & Deary, I J 2016, ' Platelet-Related Variants Identified by Exomechip Meta-analysis in 157,293 Individuals ', American Journal of Human Genetics, vol. 99, no. 1, pp. 40-55 . https://doi.org/10.1016/j.ajhg.2016.05.005 The American Journal of Human Genetics |
| ISSN: | 1537-6605 0002-9297 |
| DOI: | 10.1016/j.ajhg.2016.05.005 |
| Popis: | Platelet production, maintenance, and clearance are tightly controlled processes indicative of platelets' important roles in hemostasis and thrombosis. Platelets are common targets for primary and secondary prevention of several conditions. They are monitored clinically by complete blood counts, specifically with measurements of platelet count (PLT) and mean platelet volume (MPV). Identifying genetic effects on PLT and MPV can provide mechanistic insights into platelet biology and their role in disease. Therefore, we formed the Blood Cell Consortium (BCX) to perform a large-scale meta-analysis of Exomechip association results for PLT and MPV in 157,293 and 57,617 individuals, respectively. Using the low-frequency/rare coding variant-enriched Exomechip genotyping array, we sought to identify genetic variants associated with PLT and MPV. In addition to confirming 47 known PLT and 20 known MPV associations, we identified 32 PLT and 18 MPV associations not previously observed in the literature across the allele frequency spectrum, including rare large effect (FCER1A), low-frequency (IQGAP2, MAP1A, LY75), and common (ZMIZ2, SMG6, PEAR1, ARFGAP3/PACSIN2) variants. Several variants associated with PLT/MPV (PEAR1, MRVI1, PTGES3) were also associated with platelet reactivity. In concurrent BCX analyses, there was overlap of platelet-associated variants with red (MAP1A, TMPRSS6, ZMIZ2) and white (PEAR1, ZMIZ2, LY75) blood cell traits, suggesting common regulatory pathways with shared genetic architecture among these hematopoietic lineages. Our large-scale Exomechip analyses identified previously undocumented associations with platelet traits and further indicate that several complex quantitative hematological, lipid, and cardiovascular traits share genetic factors. |
| Databáze: | OpenAIRE |
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