A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Platelet-Related Variants Identified by Exomechip Meta-analysis in 157,293 Individuals
Tekijät: Eicher JD, Chami N, Kacprowski T, Nomura A, Chen MH, Yanek LR, Tajuddin SM, Schick UM, Slater AJ, Pankratz N, Polfus L, Schurmann C, Giri A, Brody JA, Lange LA, Manichaikul A, Hill WD, Pazoki R, Elliot P, Evangelou E, Tzoulaki I, Gao H, Vergnaud AC, Mathias RA, Becker DM, Becker LC, Burt A, Crosslin DR, Lyytikainen LP, Nikus K, Hernesniemi J, Kahonen M, Raitoharju E, Mononen N, Raitakari OT, Lehtimaki T, Cushman M, Zakai NA, Nickerson DA, Raffield LM, Quarells R, Willer CJ, Peloso GM, Abecasis GR, Liu DJJ, Deloukas P, Samani NJ, Schunkert H, Erdmann J, Fornage M, Richard M, Tardif JC, Rioux JD, Dube MP, de Denus S, Lu YC, Bottinger EP, Loos RJF, Smith AV, Harris TB, Launer LJ, Gudnason V, Edwards DRV, Torstenson ES, Liu YM, Tracy RP, Rotter JI, Rich SS, Highland HM, Boerwinkle E, Li J, Lange E, Wilson JG, Mihailov E, Magi R, Hirschhorn J, Metspalu A, Esko T, Vacchi-Suzzi C, Nalls MA, Zonderman AB, Evans MK, Engstrom 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, Volker U, Thiele T, Volzke 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
Kustantaja: CELL PRESS
Julkaisuvuosi: 2016
Journal: American Journal of Human Genetics
Tietokannassa oleva lehden nimi: AMERICAN JOURNAL OF HUMAN GENETICS
Lehden akronyymi: AM J HUM GENET
Vuosikerta: 99
Numero: 1
Aloitussivu: 40
Lopetussivu: 55
Sivujen määrä: 16
ISSN: 0002-9297
DOI: https://doi.org/10.1016/j.ajhg.2016.05.005
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.
