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Platelet-Related Variants Identified by Exomechip Meta-analysis in 157,293 Individuals.
Thursday,2016-08-18 16:04 America/Los_Angeles — zdrager
| Title | Platelet-Related Variants Identified by Exomechip Meta-analysis in 157,293 Individuals. |
| Publication Type | Journal Article |
| Year of Publication | 2016 |
| Authors | Eicher, JD, Chami, N, Kacprowski, T, Nomura, A, Chen, M-H, Yanek, LR, Tajuddin, SM, Schick, UM, Slater, AJ, Pankratz, N, Polfus, L, Schurmann, C, Giri, A, Brody, JA, Lange, LA, Manichaikul, A, W Hill, D, Pazoki, R, Elliot, P, Evangelou, E, Tzoulaki, I, Gao, H, Vergnaud, A-C, Mathias, RA, Becker, DM, Becker, LC, Burt, A, Crosslin, DR, Lyytikäinen, L-P, Nikus, K, Hernesniemi, J, Kähönen, M, Raitoharju, E, Mononen, N, Raitakari, OT, Lehtimäki, T, Cushman, M, Zakai, NA, Nickerson, DA, Raffield, LM, Quarells, R, Willer, CJ, Peloso, GM, Abecasis, GR, Liu, DJ, Deloukas, P, Samani, NJ, Schunkert, H, Erdmann, J, Fornage, M, Richard, M, Tardif, J-C, Rioux, JD, Dubé, M-P, de Denus, S, Lu, Y, Bottinger, EP, Loos, RJF, Smith, AVernon, Harris, TB, Launer, LJ, Gudnason, V, Edwards, DRVelez, Torstenson, ES, Liu, Y, Tracy, RP, Rotter, JI, Rich, SS, Highland, HM, Boerwinkle, E, Li, J, Lange, E, Wilson, JG, Mihailov, E, Mägi, R, Hirschhorn, J, Metspalu, A, Esko, T, Vacchi-Suzzi, C, Nalls, MA, Zonderman, AB, Evans, MK, Engström, G, Orho-Melander, M, Melander, O, O'Donoghue, ML, Waterworth, DM, Wallentin, L, White, HD, Floyd, JS, Bartz, TM, Rice, KM, Psaty, BM, Starr, JM, Liewald, DCM, Hayward, C, Deary, IJ, Greinacher, A, Völker, U, Thiele, T, Völzke, H, van Rooij, FJA, Uitterlinden, AG, Franco, OH, Dehghan, A, Edwards, TL, Ganesh, SK, Kathiresan, S, Faraday, N, Auer, PL, Reiner, AP, Lettre, G, Johnson, AD |
| Corporate/Institutional Authors | Global Lipids Genetics Consortium, CARDIoGRAM Exome Consortium, Myocardial Infarction Genetics Consortium |
| Journal | Am J Hum Genet |
| Volume | 99 |
| Issue | 1 |
| Pagination | 40-55 |
| Date Published | 2016 Jul 7 |
| ISSN | 1537-6605 |
| Abstract | <p>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.</p> |
| DOI | 10.1016/j.ajhg.2016.05.005 |
| Alternate Journal | Am. J. Hum. Genet. |
| PubMed ID | 27346686 |
| PubMed Central ID | PMC5005441 |
| Grant List | N01 HC025195 / HC / NHLBI NIH HHS / United States N01 HC095159 / HC / NHLBI NIH HHS / United States P30 DK063491 / DK / NIDDK NIH HHS / United States R01 HD074711 / HD / NICHD NIH HHS / United States R01 HL059367 / HL / NHLBI NIH HHS / United States R01 HL086694 / HL / NHLBI NIH HHS / United States R01 HL087641 / HL / NHLBI NIH HHS / United States R01 HL087698 / HL / NHLBI NIH HHS / United States R01 HL112064 / HL / NHLBI NIH HHS / United States RC2 HL102419 / HL / NHLBI NIH HHS / United States U01 HG004402 / HG / NHGRI NIH HHS / United States U01 HG004603 / HG / NHGRI NIH HHS / United States U01 HL072518 / HL / NHLBI NIH HHS / United States UL1 TR000124 / TR / NCATS NIH HHS / United States UL1 TR000445 / TR / NCATS NIH HHS / United States |