| Literature DB >> 27346686 |
John D Eicher1, Nathalie Chami2, Tim Kacprowski3, Akihiro Nomura4, Ming-Huei Chen1, Lisa R Yanek5, Salman M Tajuddin6, Ursula M Schick7, Andrew J Slater8, Nathan Pankratz9, Linda Polfus10, Claudia Schurmann7, Ayush Giri11, Jennifer A Brody12, Leslie A Lange13, Ani Manichaikul14, W David Hill15, Raha Pazoki16, Paul Elliot17, Evangelos Evangelou18, Ioanna Tzoulaki18, He Gao17, Anne-Claire Vergnaud17, Rasika A Mathias19, Diane M Becker5, Lewis C Becker20, Amber Burt21, David R Crosslin22, Leo-Pekka Lyytikäinen23, Kjell Nikus24, Jussi Hernesniemi25, Mika Kähönen26, Emma Raitoharju23, Nina Mononen23, Olli T Raitakari27, Terho Lehtimäki23, Mary Cushman28, Neil A Zakai28, Deborah A Nickerson29, Laura M Raffield13, Rakale Quarells30, Cristen J Willer31, Gina M Peloso32, Goncalo R Abecasis33, Dajiang J Liu34, Panos Deloukas35, Nilesh J Samani36, Heribert Schunkert37, Jeanette Erdmann38, Myriam Fornage39, Melissa Richard39, Jean-Claude Tardif2, John D Rioux2, Marie-Pierre Dube2, Simon de Denus40, Yingchang Lu41, Erwin P Bottinger41, Ruth J F Loos41, Albert Vernon Smith42, Tamara B Harris43, Lenore J Launer43, Vilmundur Gudnason42, Digna R Velez Edwards44, Eric S Torstenson11, Yongmei Liu45, Russell P Tracy46, Jerome I Rotter47, Stephen S Rich14, Heather M Highland48, Eric Boerwinkle49, Jin Li50, Ethan Lange51, James G Wilson52, Evelin Mihailov53, Reedik Mägi53, Joel Hirschhorn54, Andres Metspalu53, Tõnu Esko55, Caterina Vacchi-Suzzi56, Mike A Nalls57, Alan B Zonderman6, Michele K Evans6, Gunnar Engström58, Marju Orho-Melander58, Olle Melander58, Michelle L O'Donoghue59, Dawn M Waterworth60, Lars Wallentin61, Harvey D White62, James S Floyd12, Traci M Bartz63, Kenneth M Rice63, Bruce M Psaty64, J M Starr65, David C M Liewald15, Caroline Hayward66, Ian J Deary15, Andreas Greinacher67, Uwe Völker3, Thomas Thiele67, Henry Völzke68, Frank J A van Rooij16, André G Uitterlinden69, Oscar H Franco16, Abbas Dehghan16, Todd L Edwards11, Santhi K Ganesh70, Sekar Kathiresan71, Nauder Faraday72, Paul L Auer73, Alex P Reiner74, Guillaume Lettre2, Andrew D Johnson75.
Abstract
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. Published by Elsevier Inc.Entities:
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Year: 2016 PMID： 27346686 PMCID： PMC5005441 DOI： 10.1016/j.ajhg.2016.05.005
Source DB: PubMed Journal: Am J Hum Genet ISSN： 0002-9297 Impact factor: 11.043