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Platelet Genomics

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Platelets in Thrombotic and Non-Thrombotic Disorders

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Abstract

Human platelets are anucleate cells that contain no genomic DNA although they contain both mRNAs and microRNAs derived from precursor megakaryocytes. Nonetheless, genetic variability encompassed within both intronic and exonic sequences are clearly implicated in a wide range of functional parameters known to regulate gene expression and protein function, with concomitant effects on platelet reactivity, volume, peripheral counts, and cellular responsiveness (Hematol Oncol Clin North Am 27:443–463, 2013; Semin Thromb Hemost 39:291–305, 2013; Curr Opin Hematol 19:371–379, 2012). In this chapter, we will review the current status of genetic variations that have been implicated in functional platelet responsiveness, many of which have recently been identified using genome-wide association studies (GWAS) (Genes 5:51–64, 2014; Nat Rev Genet 11:241–246, 2010; Curr Opin Genet Dev 23:339–344, 2013). For synergistic information relevant to platelet genetics, the reader should refer to accompanying chapters on platelet mRNAs (Rowley et al. 2017), platelet noncoding RNAs (Edelstein and Bray 2017), and transcriptomic changes associated with thrombotic risk (Gnatenko et al. 2017).

Many genetic variants have subtle effects and it is likely that complex platelet-related phenotypes associated with cerebro- or cardiovascular risk result from additive effects from multiple loci, contributing to a final common pathway for defective platelet functional and clinical outcome (J Thromb Haemost 5:188–195, 2007; Curr Vasc Pharmacol 9:479–489, 2011; J Thromb Thrombolysis 32:201–208, 2011). Thus, a single subtle effect may be difficult to delineate or consistently reproduce across cohorts. In addition, other confounding variables (e.g., age, sex, body mass index, alcohol consumption, concomitant drugs, nutritional status, and environmental pollutants) may also affect platelet function (Thromb Haemost 105:S60–S66, 2011). Thus, well-defined phenotypes provide the most informative outcomes. Additionally, GWAS with large cohort sizes provide the most robust information relevant for reliable identification of new genetic variations with subtle effect(s) on platelet functional parameters (Fig. 1).

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References

  • Aalto-Setala K, Karhunen PJ, Mikkelsson J, Niemela K (2005) The effect of glycoprotein IIIa PIA 1/A2 polymorphism on the PFA-100 response to GP IIb IIa receptor inhibitors-the importance of anticoagulants used. J Thromb Thrombolysis 20(1):57–63

    Article  PubMed  CAS  Google Scholar 

  • Albers CA, Cvejic A, Favier R, Bouwmans EE, Alessi MC, Bertone P, Jordan G, Kettleborough RN, Kiddle G, Kostadima M, Read RJ, Sipos B, Sivapalaratnam S, Smethurst PA, Stephens J, Voss K, Nurden A, Rendon A, Nurden P, Ouwehand WH (2011) Exome sequencing identifies NBEAL2 as the causative gene for gray platelet syndrome. Nat Genet 43(8):735–737

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Albers CA, Paul DS, Schulze H, Freson K, Stephens JC, Smethurst PA, Jolley JD, Cvejic A, Kostadima M, Bertone P, Breuning MH, Debili N, Deloukas P, Favier R, Fiedler J, Hobbs CM, Huang N, Hurles ME, Kiddle G, Krapels I, Nurden P, Ruivenkamp CA, Sambrook JG, Smith K, Stemple DL, Strauss G, Thys C, van Geet C, Newbury-Ecob R, Ouwehand WH, Ghevaert C (2012) Compound inheritance of a low-frequency regulatory SNP and a rare null mutation in exon-junction complex subunit RBM8A causes TAR syndrome. Nat Genet 44(4):435–439, s431–s432

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Albers CA, Newbury-Ecob R, Ouwehand WH, Ghevaert C (2013) New insights into the genetic basis of TAR (thrombocytopenia-absent radii) syndrome. Curr Opin Genet Dev 23(3):316–323

    Article  CAS  PubMed  Google Scholar 

  • Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, Ramirez C, Cavallari U, Trabetti E, Sabate M, Jimenez-Quevedo P, Hernandez R, Moreno R, Escaned J, Alfonso F, Banuelos C, Costa MA, Bass TA, Pignatti PF, Macaya C (2005) Lack of association between the P2Y12 receptor gene polymorphism and platelet response to clopidogrel in patients with coronary artery disease. Thromb Res 116(6):491–497

    Article  CAS  PubMed  Google Scholar 

  • Arnaud E, Nicaud V, Poirier O, Rendu F, Alhenc-Gelas M, Fiessinger JN, Emmerich J, Aiach M (2000) Protective effect of a thrombin receptor (protease-activated receptor 1) gene polymorphism toward venous thromboembolism. Arterioscler Thromb Vasc Biol 20(2):585–592

    Article  CAS  PubMed  Google Scholar 

  • Azab B, Torbey E, Singh J, Akerman M, Khoueiry G, McGinn JT, Widmann WD, Lafferty J (2011) Mean platelet volume/platelet count ratio as a predictor of long-term mortality after non-ST-elevation myocardial infarction. Platelets 22(8):557–566

    Article  CAS  PubMed  Google Scholar 

  • Bahou WF (2013) Genetic dissection of platelet function in health and disease using systems biology. Hematol Oncol Clin North Am 27(3):443–463

    Article  PubMed  PubMed Central  Google Scholar 

  • Balduini CL, Savoia A (2012) Genetics of familial forms of thrombocytopenia. Hum Genet 131(12):1821–1832

    Article  CAS  PubMed  Google Scholar 

  • Basciano PA, Bussel J, Hafeez Z, Christos PJ, Giannakakou P (2013) The beta 1 tubulin R307H single nucleotide polymorphism is associated with treatment failures in immune thrombocytopenia (ITP). Br J Haematol 160(2):237–243

    Article  CAS  PubMed  Google Scholar 

  • Bath PM, Butterworth RJ (1996) Platelet size: measurement, physiology and vascular disease. Blood Coagul Fibrinolysis 7(2):157–161

    Article  CAS  PubMed  Google Scholar 

  • Bath PM, Gladwin AM, Carden N, Martin JF (1994) Megakaryocyte DNA content is increased in patients with coronary artery atherosclerosis. Cardiovasc Res 28(9):1348–1352

    Article  CAS  PubMed  Google Scholar 

  • Begonja AJ, Pluthero FG (2015) FlnA binding to PACSIN2 F-BAR domain regulates membrane tubulation in megakaryocytes and platelets. Blood 126(1):80–88

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bluteau D, Balduini A, Balayn N, Currao M, Nurden P, Deswarte C, Leverger G, Noris P, Perrotta S, Solary E, Vainchenker W, Debili N, Favier R, Raslova H (2014) Thrombocytopenia-associated mutations in the ANKRD26 regulatory region induce MAPK hyperactivation. J Clin Invest 124(2):580–591

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bunimov N, Fuller N, Hayward CP (2013) Genetic loci associated with platelet traits and platelet disorders. Semin Thromb Hemost 39(3):291–305

    Article  CAS  PubMed  Google Scholar 

  • Carty CL, Keene KL, Cheng YC, Meschia JF, Chen WM, Nalls M, Bis JC, Kittner SJ, Rich SS, Tajuddin S, Zonderman AB, Evans MK, Langefeld CD, Gottesman R, Mosley TH, Shahar E, Woo D, Yaffe K, Liu Y, Sale MM, Dichgans M, Malik R, Longstreth WT Jr, Mitchell BD, Psaty BM, Kooperberg C, Reiner A, Worrall BB, Fornage M (2015) Meta-analysis of genome-wide association studies identifies genetic risk factors for stroke in African Americans. Stroke 46(8):2063–2068

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cavallari U, Trabetti E, Malerba G, Biscuola M, Girelli D, Olivieri O, Martinelli N, Angiolillo DJ, Corrocher R, Pignatti PF (2007) Gene sequence variations of the platelet P2Y12 receptor are associated with coronary artery disease. BMC Med Genet 8:59

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Chami N, Lettre G (2014) Lessons and Implications from genome-wide association studies (GWAS) findings of blood cell phenotypes. Genes 5(1):51–64

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Chu SG, Becker RC, Berger PB, Bhatt DL, Eikelboom JW, Konkle B, Mohler ER, Reilly MP, Berger JS (2010) Mean platelet volume as a predictor of cardiovascular risk: a systematic review and meta-analysis. J Thromb Haemost 8(1):148–156

    Article  CAS  PubMed  Google Scholar 

  • Croft SA, Samani NJ, Teare MD, Hampton KK, Steeds RP, Channer KS, Daly ME (2001) Novel platelet membrane glycoprotein VI dimorphism is a risk factor for myocardial infarction. Circulation 104(13):1459–1463

    Article  CAS  PubMed  Google Scholar 

  • Cui H, Lin S, Chen X, Gao W, Li X, Zhou H, Du W, Wang S, Zhao R (2015) Correlation between SNPs in candidate genes and verifynow-detected platelet responsiveness to aspirin and clopidogrel treatment. Cardiovasc Drugs Ther 29(2):137–146

    Article  CAS  PubMed  Google Scholar 

  • Cuisset T, Loosveld M, Morange PE, Quilici J, Moro PJ, Saut N, Gaborit B, Castelli C, Beguin S, Grosdidier C, Fourcade L, Bonnet JL, Alessi MC (2012) CYP2C19*2 and *17 alleles have a significant impact on platelet response and bleeding risk in patients treated with prasugrel after acute coronary syndrome. JACC Cardiovasc Interv 5(12):1280–1287

    Article  PubMed  Google Scholar 

  • Dalby Kristensen S, Bath PM, Martin JF (1988) The bleeding time is inversely related to megakaryocyte nuclear DNA content and size in man. Thromb Haemost 59(3):357–359

    CAS  PubMed  Google Scholar 

  • Daly AK (2010) Genome-wide association studies in pharmacogenomics. Nat Rev Genet 11(4):241–246

    Article  CAS  PubMed  Google Scholar 

  • De R, Bush WS, Moore JH (2014) Bioinformatics challenges in genome-wide association studies (GWAS). Methods Mol Biol 1168:63–81

    Article  PubMed  Google Scholar 

  • Deppermann C, Cherpokova D, Nurden P, Schulz JN, Thielmann I, Kraft P, Vogtle T, Kleinschnitz C, Dutting S, Krohne G, Eming SA, Nurden AT, Eckes B, Stoll G, Stegner D, Nieswandt B (2013) Gray platelet syndrome and defective thrombo-inflammation in Nbeal2-deficient mice. J Clin Invest. doi:10.1172/jci69210

  • Dupont A, Fontana P, Bachelot-Loza C, Reny JL, Bieche I, Desvard F, Aiach M, Gaussem P (2003) An intronic polymorphism in the PAR-1 gene is associated with platelet receptor density and the response to SFLLRN. Blood 101(5):1833–1840

    Article  CAS  PubMed  Google Scholar 

  • Edelstein LC, Bray PF (2017) Noncoding RNAs in platelet biology. In: Gresele P et al (eds) Platelets in thrombotic and non-thrombotic disorders: pathophysiology, pharmacology and therapeutics. Springer, Cham, pp 239–252

    Google Scholar 

  • Falet H (2013) New insights into the versatile roles of platelet FlnA. Platelets 24(1):1–5

    Article  CAS  PubMed  Google Scholar 

  • Faraday N, Becker DM, Becker LC (2007a) Pharmacogenomics of platelet responsiveness to aspirin. Pharmacogenomics 8(10):1413–1425

    Article  CAS  PubMed  Google Scholar 

  • Faraday N, Yanek LR, Mathias R, Herrera-Galeano JE, Vaidya D, Moy TF, Fallin MD, Wilson AF, Bray PF, Becker LC, Becker DM (2007b) Heritability of platelet responsiveness to aspirin in activation pathways directly and indirectly related to cyclooxygenase-1. Circulation 115(19):2490–2496

    Article  CAS  PubMed  Google Scholar 

  • Faraday N, Yanek LR, Yang XP, Mathias R, Herrera-Galeano JE, Suktitipat B, Qayyum R, Johnson AD, Chen MH, Tofler GH, Ruczinski I, Friedman AD, Gylfason A, Thorsteinsdottir U, Bray PF, O’Donnell CJ, Becker DM, Becker LC (2011) Identification of a specific intronic PEAR1 gene variant associated with greater platelet aggregability and protein expression. Blood 118(12):3367–3375

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fiedler J, Strauss G, Wannack M, Schwiebert S, Seidel K, Henning K, Klopocki E, Schmugge M, Gaedicke G, Schulze H (2012) Two patterns of thrombopoietin signaling suggest no coupling between platelet production and thrombopoietin reactivity in thrombocytopenia-absent radii syndrome. Haematologica 97(1):73–81

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Floyd CN, Ferro A (2012) The platelet fibrinogen receptor: from megakaryocyte to the mortuary. JRSM Cardiovasc Dis 1(2). doi:10.1258/cvd.2012.012007

  • Fontana P, Gaussem P, Aiach M, Fiessinger JN, Emmerich J, Reny JL (2003) P2Y12 H2 haplotype is associated with peripheral arterial disease: a case-control study. Circulation 108(24):2971–2973

    Article  PubMed  Google Scholar 

  • Freedman JE (2006) The aspirin resistance controversy: clinical entity or platelet heterogeneity? Circulation 113(25):2865–2867

    Article  PubMed  Google Scholar 

  • Frelinger AL 3rd, Furman MI, Linden MD, Li Y, Fox ML, Barnard MR, Michelson AD (2006) Residual arachidonic acid-induced platelet activation via an adenosine diphosphate-dependent but cyclooxygenase-1- and cyclooxygenase-2-independent pathway: a 700-patient study of aspirin resistance. Circulation 113(25):2888–2896

    Article  CAS  PubMed  Google Scholar 

  • Freson K, Izzi B, Van Geet C (2012) From genetics to epigenetics in platelet research. Thromb Res 129(3):325–329

    Article  CAS  PubMed  Google Scholar 

  • Freson K, Wijgaerts A, van Geet C (2014) Update on the causes of platelet disorders and functional consequences. Int J Lab Hematol 36(3):313–325

    Article  CAS  PubMed  Google Scholar 

  • Gasparyan AY, Ayvazyan L, Mikhailidis DP, Kitas GD (2011) Mean platelet volume: a link between thrombosis and inflammation? Curr Pharm Des 17(1):47–58

    Article  CAS  PubMed  Google Scholar 

  • Geisler T, Schaeffeler E, Dippon J, Winter S, Buse V, Bischofs C, Zuern C, Moerike K, Gawaz M, Schwab M (2008) CYP2C19 and nongenetic factors predict poor responsiveness to clopidogrel loading dose after coronary stent implantation. Pharmacogenomics 9(9):1251–1259

    Article  CAS  PubMed  Google Scholar 

  • Geisler T, Schaeffeler E, Gawaz M, Schwab M (2013) Genetic variation of platelet function and pharmacology: an update of current knowledge. Thromb Haemost 110(5):876–887

    Article  CAS  PubMed  Google Scholar 

  • Gieger C, Radhakrishnan A, Cvejic A, Tang W, Porcu E, Pistis G, Serbanovic-Canic J, Elling U, Goodall AH, Labrune Y, Lopez LM, Magi R, Meacham S, Okada Y, Pirastu N, Sorice R, Teumer A, Voss K, Zhang W, Ramirez-Solis R, Bis JC, Ellinghaus D, Gogele M, Hottenga JJ, Langenberg C, Kovacs P, O’Reilly PF, Shin SY, Esko T, Hartiala J, Kanoni S, Murgia F, Parsa A, Stephens J, van der Harst P, van der Schoot Ellen C, Allayee H, Attwood A, Balkau B, Bastardot F, Basu S, Baumeister SE, Biino G, Bomba L, Bonnefond A, Cambien F, Chambers JC, Cucca F, D'Adamo P, Davies G, de Boer RA, de Geus EJ, Doring A, Elliott P, Erdmann J, Evans DM, Falchi M, Feng W, Folsom AR, Frazer IH, Gibson QD, Glazer NL, Hammond C, Hartikainen AL, Heckbert SR, Hengstenberg C, Hersch M, Illig T, Loos RJ, Jolley J, Khaw KT, Kuhnel B, Kyrtsonis MC, Lagou V, Lloyd-Jones H, Lumley T, Mangino M, Maschio A, Mateo Leach I, McKnight B, Memari Y, Mitchell BD, Montgomery GW, Nakamura Y, Nauck M, Navis G, Nothlings U, Nolte IM, Porteous DJ, Pouta A, Pramstaller PP, Pullat J, Ring SM, Rotter JI, Ruggiero D, Ruokonen A, Sala C, Samani NJ, Sambrook J, Schlessinger D, Schreiber S, Schunkert H, Scott J, Smith NL, Snieder H, Starr JM, Stumvoll M, Takahashi A, Tang WH, Taylor K, Tenesa A, Lay Thein S, Tonjes A, Uda M, Ulivi S, van Veldhuisen DJ, Visscher PM, Volker U, Wichmann HE, Wiggins KL, Willemsen G, Yang TP, Hua Zhao J, Zitting P, Bradley JR, Dedoussis GV, Gasparini P, Hazen SL, Metspalu A, Pirastu M, Shuldiner AR, Joost van Pelt L, Zwaginga JJ, Boomsma DI, Deary IJ, Franke A, Froguel P, Ganesh SK, Jarvelin MR, Martin NG, Meisinger C, Psaty BM, Spector TD, Wareham NJ, Akkerman JW, Ciullo M, Deloukas P, Greinacher A, Jupe S, Kamatani N, Khadake J, Kooner JS, Penninger J, Prokopenko I, Stemple D, Toniolo D, Wernisch L, Sanna S, Hicks AA, Rendon A, Ferreira MA, Ouwehand WH, Soranzo N (2011) New gene functions in megakaryopoiesis and platelet formation. Nature 480(7376):201–208

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gnatenko DV, Li Z, Bahou WF (2017) Gene regulation of platelet function. In: Gresele P et al (eds) Platelets in thrombotic and non-thrombotic disorders: pathophysiology, pharmacology and therapeutics. Springer, Cham, pp 1053–1067

    Google Scholar 

  • Grosdidier C, Quilici J, Loosveld M, Camoin L, Moro PJ, Saut N, Gaborit B, Pankert M, Cohen W, Lambert M, Beguin S, Morange PE, Bonnet JL, Alessi MC, Cuisset T (2013) Effect of CYP2C19*2 and *17 genetic variants on platelet response to clopidogrel and prasugrel maintenance dose and relation to bleeding complications. Am J Cardiol 111(7):985–990

    Article  CAS  PubMed  Google Scholar 

  • Gunay-Aygun M, Falik-Zaccai TC, Vilboux T, Zivony-Elboum Y, Gumruk F, Cetin M, Khayat M, Boerkoel CF, Kfir N, Huang Y, Maynard D, Dorward H, Berger K, Kleta R, Anikster Y, Arat M, Freiberg AS, Kehrel BE, Jurk K, Cruz P, Mullikin JC, White JG, Huizing M, Gahl WA (2011) NBEAL2 is mutated in gray platelet syndrome and is required for biogenesis of platelet alpha-granules. Nat Genet 43(8):732–734

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Herrera-Galeano JE, Becker DM, Wilson AF, Yanek LR, Bray P, Vaidya D, Faraday N, Becker LC (2008) A novel variant in the platelet endothelial aggregation receptor-1 gene is associated with increased platelet aggregability. Arterioscler Thromb Vasc Biol 28(8):1484–1490

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hetherington SL, Singh RK, Lodwick D, Thompson JR, Goodall AH, Samani NJ (2005) Dimorphism in the P2Y1 ADP receptor gene is associated with increased platelet activation response to ADP. Arterioscler Thromb Vasc Biol 25(1):252–257

    CAS  PubMed  Google Scholar 

  • Hines LM, Tabakoff B (2005) Platelet adenylyl cyclase activity: a biological marker for major depression and recent drug use. Biol Psychiatry 58(12):955–962

    Article  CAS  PubMed  Google Scholar 

  • Hulot JS, Bura A, Villard E, Azizi M, Remones V, Goyenvalle C, Aiach M, Lechat P, Gaussem P (2006) Cytochrome P450 2C19 loss-of-function polymorphism is a major determinant of clopidogrel responsiveness in healthy subjects. Blood 108(7):2244–2247

    Article  CAS  PubMed  Google Scholar 

  • Israels SJ, Rand ML (2013) What we have learned from inherited platelet disorders. Pediatr Blood Cancer 60(Suppl 1):S2–7

    Article  CAS  PubMed  Google Scholar 

  • Johnson AD, Yanek LR, Chen MH, Faraday N, Larson MG, Tofler G, Lin SJ, Kraja AT, Province MA, Yang Q, Becker DM, O’Donnell CJ, Becker LC (2010) Genome-wide meta-analyses identifies seven loci associated with platelet aggregation in response to agonists. Nat Genet 42(7):608–613

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jones CI, Bray S, Garner SF, Stephens J, de Bono B, Angenent WG, Bentley D, Burns P, Coffey A, Deloukas P, Earthrowl M, Farndale RW, Hoylaerts MF, Koch K, Rankin A, Rice CM, Rogers J, Samani NJ, Steward M, Walker A, Watkins NA, Akkerman JW, Dudbridge F, Goodall AH, Ouwehand WH (2009) A functional genomics approach reveals novel quantitative trait loci associated with platelet signaling pathways. Blood 114(7):1405–1416

    Article  CAS  PubMed  Google Scholar 

  • Kahr WH, Hinckley J, Li L, Schwertz H, Christensen H, Rowley JW, Pluthero FG, Urban D, Fabbro S, Nixon B, Gadzinski R, Storck M, Wang K, Ryu GY, Jobe SM, Schutte BC, Moseley J, Loughran NB, Parkinson J, Weyrich AS, Di Paola J (2011) Mutations in NBEAL2, encoding a BEACH protein, cause gray platelet syndrome. Nat Genet 43(8):738–740

    Article  CAS  PubMed  Google Scholar 

  • Kamatani Y, Matsuda K, Okada Y, Kubo M, Hosono N, Daigo Y, Nakamura Y, Kamatani N (2010) Genome-wide association study of hematological and biochemical traits in a Japanese population. Nat Genet 42(3):210–215

    Article  CAS  PubMed  Google Scholar 

  • Kathiresan S, Voight BF, Purcell S, Musunuru K, Ardissino D, Mannucci PM, Anand S, Engert JC, Samani NJ, Schunkert H, Erdmann J, Reilly MP, Rader DJ, Morgan T, Spertus JA, Stoll M, Girelli D, McKeown PP, Patterson CC, Siscovick DS, O’Donnell CJ, Elosua R, Peltonen L, Salomaa V, Schwartz SM, Melander O, Altshuler D, Ardissino D, Merlini PA, Berzuini C, Bernardinelli L, Peyvandi F, Tubaro M, Celli P, Ferrario M, Fetiveau R, Marziliano N, Casari G, Galli M, Ribichini F, Rossi M, Bernardi F, Zonzin P, Piazza A, Mannucci PM, Schwartz SM, Siscovick DS, Yee J, Friedlander Y, Elosua R, Marrugat J, Lucas G, Subirana I, Sala J, Ramos R, Kathiresan S, Meigs JB, Williams G, Nathan DM, MacRae CA, O’Donnell CJ, Salomaa V, Havulinna AS, Peltonen L, Melander O, Berglund G, Voight BF, Kathiresan S, Hirschhorn JN, Asselta R, Duga S, Spreafico M, Musunuru K, Daly MJ, Purcell S, Voight BF, Purcell S, Nemesh J, Korn JM, McCarroll SA, Schwartz SM, Yee J, Kathiresan S, Lucas G, Subirana I, Elosua R, Surti A, Guiducci C, Gianniny L, Mirel D, Parkin M, Burtt N, Gabriel SB, Samani NJ, Thompson JR, Braund PS, Wright BJ, Balmforth AJ, Ball SG, Hall A, Schunkert H, Erdmann J, Linsel-Nitschke P, Lieb W, Ziegler A, Konig I, Hengstenberg C, Fischer M, Stark K, Grosshennig A, Preuss M, Wichmann HE, Schreiber S, Schunkert H, Samani NJ, Erdmann J, Ouwehand W, Hengstenberg C, Deloukas P, Scholz M, Cambien F, Reilly MP, Li M, Chen Z, Wilensky R, Matthai W, Qasim A, Hakonarson HH, Devaney J, Burnett MS, Pichard AD, Kent KM, Satler L, Lindsay JM, Waksman R, Knouff CW, Waterworth DM, Walker MC, Mooser V, Epstein SE, Rader DJ, Scheffold T, Berger K, Stoll M, Huge A, Girelli D, Martinelli N, Olivieri O, Corrocher R, Morgan T, Spertus JA, McKeown P, Patterson CC, Schunkert H, Erdmann E, Linsel-Nitschke P, Lieb W, Ziegler A, Konig IR, Hengstenberg C, Fischer M, Stark K, Grosshennig A, Preuss M, Wichmann HE, Schreiber S, Holm H, Thorleifsson G, Thorsteinsdottir U, Stefansson K, Engert JC, Do R, Xie C, Anand S, Kathiresan S, Ardissino D, Mannucci PM, Siscovick D, O’Donnell CJ, Samani NJ, Melander O, Elosua R, Peltonen L, Salomaa V, Schwartz SM, Altshuler D (2009) Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants. Nat Genet 41(3):334–341

    Article  CAS  PubMed  Google Scholar 

  • Kim Y, Suktitipat B, Yanek LR, Faraday N, Wilson AF, Becker DM, Becker LC, Mathias RA (2013) Targeted deep resequencing identifies coding variants in the PEAR1 gene that play a role in platelet aggregation. PLoS One 8(5), e64179

    Article  PubMed  PubMed Central  Google Scholar 

  • Klopocki E, Schulze H, Strauss G, Ott CE, Hall J, Trotier F, Fleischhauer S, Greenhalgh L, Newbury-Ecob RA, Neumann LM, Habenicht R, Konig R, Seemanova E, Megarbane A, Ropers HH, Ullmann R, Horn D, Mundlos S (2007) Complex inheritance pattern resembling autosomal recessive inheritance involving a microdeletion in thrombocytopenia-absent radius syndrome. Am J Hum Genet 80(2):232–240

    Article  CAS  PubMed  Google Scholar 

  • Kunicki TJ, Kritzik M, Annis DS, Nugent DJ (1997) Hereditary variation in platelet integrin alpha 2 beta 1 density is associated with two silent polymorphisms in the alpha 2 gene coding sequence. Blood 89(6):1939–1943

    CAS  PubMed  Google Scholar 

  • Kunicki TJ, Williams SA, Nugent DJ (2012) Genetic variants that affect platelet function. Curr Opin Hematol 19(5):371–379

    Article  CAS  PubMed  Google Scholar 

  • Kunishima S, Saito H (2010) Advances in the understanding of MYH9 disorders. Curr Opin Hematol 17(5):405–410

    Article  CAS  PubMed  Google Scholar 

  • Kunishima S, Okuno Y, Yoshida K, Shiraishi Y, Sanada M, Muramatsu H, Chiba K, Tanaka H, Miyazaki K, Sakai M, Ohtake M, Kobayashi R, Iguchi A, Niimi G, Otsu M, Takahashi Y, Miyano S, Saito H, Kojima S, Ogawa S (2013) ACTN1 mutations cause congenital macrothrombocytopenia. Am J Hum Genet 92(3):431–438

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kunishima S, Nishimura S, Suzuki H, Imaizumi M, Saito H (2014) TUBB1 mutation disrupting microtubule assembly impairs proplatelet formation and results in congenital macrothrombocytopenia. Eur J Haematol 92(4):276–282

    Article  CAS  PubMed  Google Scholar 

  • Lambert MP (2015) Update on the inherited platelet disorders. Curr Opin Hematol 22(5):460–466

    Article  CAS  PubMed  Google Scholar 

  • Lance MD, Sloep M, Henskens YM, Marcus MA (2012) Mean platelet volume as a diagnostic marker for cardiovascular disease: drawbacks of preanalytical conditions and measuring techniques. Clin Appl Thromb Hemost 18(6):561–568

    Article  PubMed  Google Scholar 

  • Landolt-Marticorena C, Kahr WH (2014) Inherited macrothrombocytopenias on the rise. Blood 124(16):2473–2475

    Article  CAS  PubMed  Google Scholar 

  • Lewis JP, Horenstein RB, Ryan K, O’Connell JR, Gibson Q, Mitchell BD, Tanner K, Chai S, Bliden KP, Tantry US, Peer CJ, Figg WD, Spencer SD, Pacanowski MA, Gurbel PA, Shuldiner AR (2013a) The functional G143E variant of carboxylesterase 1 is associated with increased clopidogrel active metabolite levels and greater clopidogrel response. Pharmacogenet Genomics 23(1):1–8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lewis JP, Ryan K, O’Connell JR, Horenstein RB, Damcott CM, Gibson Q, Pollin TI, Mitchell BD, Beitelshees AL, Pakzy R, Tanner K, Parsa A, Tantry US, Bliden KP, Post WS, Faraday N, Herzog W, Gong Y, Pepine CJ, Johnson JA, Gurbel PA, Shuldiner AR (2013b) Genetic variation in PEAR1 is associated with platelet aggregation and cardiovascular outcomes. Circ Cardiovasc Genet 6(2):184–192

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lo KS, Wilson JG, Lange LA, Folsom AR, Galarneau G, Ganesh SK, Grant SF, Keating BJ, McCarroll SA, Mohler ER 3rd, O’Donnell CJ, Palmas W, Tang W, Tracy RP, Reiner AP, Lettre G (2011) Genetic association analysis highlights new loci that modulate hematological trait variation in Caucasians and African Americans. Hum Genet 129(3):307–317

    Article  PubMed  Google Scholar 

  • Manchev VT, Hilpert M, Berrou E, Elaib Z, Aouba A, Boukour S, Souquere S, Pierron G, Rameau P, Andrews R, Lanza F, Bobe R, Vainchenker W, Rosa JP, Bryckaert M, Debili N, Favier R, Raslova H (2014) A new form of macrothrombocytopenia induced by a germ-line mutation in the PRKACG gene. Blood 124(16):2554–2563

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mathias RA, Kim Y, Sung H, Yanek LR, Mantese VJ, Hererra-Galeano JE, Ruczinski I, Wilson AF, Faraday N, Becker LC, Becker DM (2010) A combined genome-wide linkage and association approach to find susceptibility loci for platelet function phenotypes in European American and African American families with coronary artery disease. BMC Med Genomics 3:22

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mattina T, Perrotta CS, Grossfeld P (2009) Jacobsen syndrome. Orphanet J Rare Dis 4:9

    Article  PubMed  PubMed Central  Google Scholar 

  • Mega JL, Close SL, Wiviott SD, Shen L, Hockett RD, Brandt JT, Walker JR, Antman EM, Macias W, Braunwald E, Sabatine MS (2009) Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med 360(4):354–362

    Article  CAS  PubMed  Google Scholar 

  • Meisinger C, Prokisch H, Gieger C, Soranzo N, Mehta D, Rosskopf D, Lichtner P, Klopp N, Stephens J, Watkins NA, Deloukas P, Greinacher A, Koenig W, Nauck M, Rimmbach C, Volzke H, Peters A, Illig T, Ouwehand WH, Meitinger T, Wichmann HE, Doring A (2009) A genome-wide association study identifies three loci associated with mean platelet volume. Am J Hum Genet 84(1):66–71

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Meyer UA, Zanger UM, Schwab M (2013) Omics and drug response. Annu Rev Pharmacol Toxicol 53:475–502

    Article  CAS  PubMed  Google Scholar 

  • Michelson AD, Furman MI, Goldschmidt-Clermont P, Mascelli MA, Hendrix C, Coleman L, Hamlington J, Barnard MR, Kickler T, Christie DJ, Kundu S, Bray PF (2000) Platelet GP IIIa Pl(A) polymorphisms display different sensitivities to agonists. Circulation 101(9):1013–1018

    Article  CAS  PubMed  Google Scholar 

  • Moshfegh K, Wuillemin WA, Redondo M, Lammle B, Beer JH, Liechti-Gallati S, Meyer BJ (1999) Association of two silent polymorphisms of platelet glycoprotein Ia/IIa receptor with risk of myocardial infarction: a case-control study. Lancet 353(9150):351–354

    Article  CAS  PubMed  Google Scholar 

  • Motovska Z, Widimsky P, Kvasnicka J, Petr R, Bilkova D, Hajkova J, Marinov I, Simek S, Kala P (2009) High loading dose of clopidogrel is unable to satisfactorily inhibit platelet reactivity in patients with glycoprotein IIIA gene polymorphism: a genetic substudy of PRAGUE-8 trial. Blood Coagul Fibrinolysis 20(4):257–262

    Article  CAS  PubMed  Google Scholar 

  • Noetzli L, Lo RW, Lee-Sherick AB, Callaghan M, Noris P, Savoia A, Rajpurkar M, Jones K, Gowan K, Balduini CL, Pecci A, Gnan C, De Rocco D, Doubek M, Li L, Lu L, Leung R, Landolt-Marticorena C, Hunger S, Heller P, Gutierrez-Hartmann A, Xiayuan L, Pluthero FG, Rowley JW, Weyrich AS, Kahr WH, Porter CC, Di Paola J (2015) Germline mutations in ETV6 are associated with thrombocytopenia, red cell macrocytosis and predisposition to lymphoblastic leukemia. Nat Genet 47(5):535–538

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nurden AT, Nurden P (2015) Inherited disorders of platelet function: selected updates. J Thromb Haemost 13(Suppl 1):S2–S9

    Article  CAS  PubMed  Google Scholar 

  • Nurden P, Debili N, Coupry I, Bryckaert M, Youlyouz-Marfak I, Sole G, Pons AC, Berrou E, Adam F, Kauskot A, Lamaziere JM, Rameau P, Fergelot P, Rooryck C, Cailley D, Arveiler B, Lacombe D, Vainchenker W, Nurden A, Goizet C (2011) Thrombocytopenia resulting from mutations in filamin A can be expressed as an isolated syndrome. Blood 118(22):5928–5937

    Article  CAS  PubMed  Google Scholar 

  • Nurden AT, Freson K, Seligsohn U (2012) Inherited platelet disorders. Haemophilia 18(Suppl 4):154–160

    Article  PubMed  Google Scholar 

  • Oh JH, Kim YK, Moon S, Kim YJ, Kim BJ (2014) Genome-wide association study identifies candidate Loci associated with platelet count in koreans. Genomics Inform 12(4):225–230

    Article  PubMed  PubMed Central  Google Scholar 

  • Ollikainen E, Mikkelsson J, Perola M, Penttila A, Karhunen PJ (2004) Platelet membrane collagen receptor glycoprotein VI polymorphism is associated with coronary thrombosis and fatal myocardial infarction in middle-aged men. Atherosclerosis 176(1):95–99

    Article  CAS  PubMed  Google Scholar 

  • Ouwehand WH (2007) Platelet genomics and the risk of atherothrombosis. J Thromb Haemost 5(Suppl 1):188–195

    Article  CAS  PubMed  Google Scholar 

  • Ouwehand WH (2009) The discovery of genes implicated in myocardial infarction. J Thromb Haemost 7(Suppl 1):305–307

    Article  CAS  PubMed  Google Scholar 

  • Owen CJ, Toze CL, Koochin A, Forrest DL, Smith CA, Stevens JM, Jackson SC, Poon MC, Sinclair GD, Leber B, Johnson PR, Macheta A, Yin JA, Barnett MJ, Lister TA, Fitzgibbon J (2008) Five new pedigrees with inherited RUNX1 mutations causing familial platelet disorder with propensity to myeloid malignancy. Blood 112(12):4639–4645

    Article  CAS  PubMed  Google Scholar 

  • Pecci A (2013) Pathogenesis and management of inherited thrombocytopenias: rationale for the use of thrombopoietin-receptor agonists. Int J Hematol 98(1):34–47

    Article  CAS  PubMed  Google Scholar 

  • Perry CG, Shuldiner AR (2013) Pharmacogenomics of anti-platelet therapy: how much evidence is enough for clinical implementation? J Hum Genet 58(6):339–345

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Quinn MJ, Topol EJ (2001) Common variations in platelet glycoproteins: pharmacogenomic implications. Pharmacogenomics 2(4):341–352

    Article  CAS  PubMed  Google Scholar 

  • Reny JL, Combescure C, Daali Y, Fontana P (2012) Influence of the paraoxonase-1 Q192R genetic variant on clopidogrel responsiveness and recurrent cardiovascular events: a systematic review and meta-analysis. J Thromb Haemost 10(7):1242–1251

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rowley JW, Manne BH, Weyrich AS (2017) The platelet transcriptome: coding RNAs. In: Gresele P et al (eds) Platelets in thrombotic and non-thrombotic disorders: pathophysiology, pharmacology and therapeutics. Springer, Cham, pp 227–238

    Google Scholar 

  • Sabatine MS, Mega JL (2014) Pharmacogenomics of antiplatelet drugs. Hematology Am Soc Hematol Educ Program 2014(1):343–347

    PubMed  Google Scholar 

  • Sangkuhl K, Klein TE, Altman RB (2010) Clopidogrel pathway. Pharmacogenet Genomics 20(7):463–465

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sankaran VG, Orkin SH (2013) Genome-wide association studies of hematologic phenotypes: a window into human hematopoiesis. Curr Opin Genet Dev 23(3):339–344

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sansanayudh N, Anothaisintawee T, Muntham D, McEvoy M, Attia J, Thakkinstian A (2014) Mean platelet volume and coronary artery disease: a systematic review and meta-analysis. Int J Cardiol 175(3):433–440

    Article  PubMed  Google Scholar 

  • Santoso S, Kunicki TJ, Kroll H, Haberbosch W, Gardemann A (1999) Association of the platelet glycoprotein Ia C807T gene polymorphism with nonfatal myocardial infarction in younger patients. Blood 93(8):2449–2453

    CAS  PubMed  Google Scholar 

  • Saposnik B, Binard S, Fenneteau O, Nurden A, Nurden P, Hurtaud-Roux MF, Schlegel N (2014) Mutation spectrum and genotype-phenotype correlations in a large French cohort of MYH9-related disorders. Mol Genet Genomic Med 2(4):297–312

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shameer K, Denny JC, Ding K, Jouni H, Crosslin DR, de Andrade M, Chute CG, Peissig P, Pacheco JA, Li R, Bastarache L, Kho AN, Ritchie MD, Masys DR, Chisholm RL, Larson EB, McCarty CA, Roden DM, Jarvik GP, Kullo IJ (2014) A genome- and phenome-wide association study to identify genetic variants influencing platelet count and volume and their pleiotropic effects. Hum Genet 133(1):95–109

    Article  PubMed  Google Scholar 

  • Shanker J, Gasparyan AY, Kitas GD, Kakkar VV (2011) Platelet function and antiplatelet therapy in cardiovascular disease: implications of genetic polymorphisms. Curr Vasc Pharmacol 9(4):479–489

    Article  CAS  PubMed  Google Scholar 

  • Sharma G, Berger JS (2011) Platelet activity and cardiovascular risk in apparently healthy individuals: a review of the data. J Thromb Thrombolysis 32(2):201–208

    Article  CAS  PubMed  Google Scholar 

  • Shuldiner AR, O’Connell JR, Bliden KP, Gandhi A, Ryan K, Horenstein RB, Damcott CM, Pakyz R, Tantry US, Gibson Q, Pollin TI, Post W, Parsa A, Mitchell BD, Faraday N, Herzog W, Gurbel PA (2009) Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy. J Am Med Assoc 302(8):849–857

    Article  CAS  Google Scholar 

  • Simon T, Verstuyft C, Mary-Krause M, Quteineh L, Drouet E, Meneveau N, Steg PG, Ferrieres J, Danchin N, Becquemont L (2009) Genetic determinants of response to clopidogrel and cardiovascular events. N Engl J Med 360(4):363–375

    Article  CAS  PubMed  Google Scholar 

  • Slowik A, Dziedzic T, Turaj W, Pera J, Glodzik-Sobanska L, Szermer P, Malecki MT, Figlewicz DA, Szczudlik A (2004) A2 alelle of GpIIIa gene is a risk factor for stroke caused by large-vessel disease in males. Stroke 35(7):1589–1593

    Article  CAS  PubMed  Google Scholar 

  • Songdej N, Rao AK (2015) Hematopoietic transcription factor mutations and inherited platelet dysfunction. F1000Prime Rep 7:66

    Google Scholar 

  • Soranzo N, Rendon A, Gieger C, Jones CI, Watkins NA, Menzel S, Doring A, Stephens J, Prokisch H, Erber W, Potter SC, Bray SL, Burns P, Jolley J, Falchi M, Kuhnel B, Erdmann J, Schunkert H, Samani NJ, Illig T, Garner SF, Rankin A, Meisinger C, Bradley JR, Thein SL, Goodall AH, Spector TD, Deloukas P, Ouwehand WH (2009a) A novel variant on chromosome 7q22.3 associated with mean platelet volume, counts, and function. Blood 113(16):3831–3837

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Soranzo N, Spector TD, Mangino M, Kuhnel B, Rendon A, Teumer A, Willenborg C, Wright B, Chen L, Li M, Salo P, Voight BF, Burns P, Laskowski RA, Xue Y, Menzel S, Altshuler D, Bradley JR, Bumpstead S, Burnett MS, Devaney J, Doring A, Elosua R, Epstein SE, Erber W, Falchi M, Garner SF, Ghori MJ, Goodall AH, Gwilliam R, Hakonarson HH, Hall AS, Hammond N, Hengstenberg C, Illig T, Konig IR, Knouff CW, McPherson R, Melander O, Mooser V, Nauck M, Nieminen MS, O’Donnell CJ, Peltonen L, Potter SC, Prokisch H, Rader DJ, Rice CM, Roberts R, Salomaa V, Sambrook J, Schreiber S, Schunkert H, Schwartz SM, Serbanovic-Canic J, Sinisalo J, Siscovick DS, Stark K, Surakka I, Stephens J, Thompson JR, Volker U, Volzke H, Watkins NA, Wells GA, Wichmann HE, Van Heel DA, Tyler-Smith C, Thein SL, Kathiresan S, Perola M, Reilly MP, Stewart AF, Erdmann J, Samani NJ, Meisinger C, Greinacher A, Deloukas P, Ouwehand WH, Gieger C (2009b) A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium. Nat Genet 41(11):1182–1190

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stevenson WS, Morel-Kopp MC, Chen Q, Liang HP, Bromhead CJ, Wright S, Turakulov R, Ng AP, Roberts AW, Bahlo M, Ward CM (2013) GFI1B mutation causes a bleeding disorder with abnormal platelet function. J Thromb Haemost 11(11):2039–2047

    Article  CAS  PubMed  Google Scholar 

  • Stockley J, Morgan NV, Bem D, Lowe GC, Lordkipanidze M, Dawood B, Simpson MA, Macfarlane K, Horner K, Leo VC, Talks K, Motwani J, Wilde JT, Collins PW, Makris M, Watson SP, Daly ME (2013) Enrichment of FLI1 and RUNX1 mutations in families with excessive bleeding and platelet dense granule secretion defects. Blood 122(25):4090–4093

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tantry US, Bliden KP, Wei C, Storey RF, Armstrong M, Butler K, Gurbel PA (2010) First analysis of the relation between CYP2C19 genotype and pharmacodynamics in patients treated with ticagrelor versus clopidogrel: the ONSET/OFFSET and RESPOND genotype studies. Circ Cardiovasc Genet 3(6):556–566

    Article  CAS  PubMed  Google Scholar 

  • Tentzeris I, Siller-Matula J, Farhan S, Jarai R, Wojta J, Huber K (2011) Platelet function variability and non-genetic causes. Thromb Haemost 105(Suppl 1):S60–S66

    Article  CAS  PubMed  Google Scholar 

  • Tijssen MR, Ghevaert C (2013) Transcription factors in late megakaryopoiesis and related platelet disorders. J Thromb Haemost 11(4):593–604

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Trenk D, Hochholzer W, Fromm MF, Chialda LE, Pahl A, Valina CM, Stratz C, Schmiebusch P, Bestehorn HP, Buttner HJ, Neumann FJ (2008) Cytochrome P450 2C19 681G > A polymorphism and high on-clopidogrel platelet reactivity associated with adverse 1-year clinical outcome of elective percutaneous coronary intervention with drug-eluting or bare-metal stents. J Am Coll Cardiol 51(20):1925–1934

    Article  CAS  PubMed  Google Scholar 

  • Vizioli L, Muscari S, Muscari A (2009) The relationship of mean platelet volume with the risk and prognosis of cardiovascular diseases. Int J Clin Pract 63(10):1509–1515

    Article  CAS  PubMed  Google Scholar 

  • von Beckerath N, von Beckerath O, Koch W, Eichinger M, Schomig A, Kastrati A (2005) P2Y12 gene H2 haplotype is not associated with increased adenosine diphosphate-induced platelet aggregation after initiation of clopidogrel therapy with a high loading dose. Blood Coagul Fibrinolysis 16(3):199–204

    Article  Google Scholar 

  • Wallentin L, James S, Storey RF, Armstrong M, Barratt BJ, Horrow J, Husted S, Katus H, Steg PG, Shah SH, Becker RC (2010) Effect of CYP2C19 and ABCB1 single nucleotide polymorphisms on outcomes of treatment with ticagrelor versus clopidogrel for acute coronary syndromes: a genetic substudy of the PLATO trial. Lancet 376(9749):1320–1328

    Article  CAS  PubMed  Google Scholar 

  • Westbury SK, Turro E, Greene D, Lentaigne C, Kelly AM, Bariana TK, Simeoni I, Pillois X, Attwood A, Austin S, Jansen SB, Bakchoul T, Crisp-Hihn A, Erber WN, Favier R, Foad N, Gattens M, Jolley JD, Liesner R, Meacham S, Millar CM, Nurden AT, Peerlinck K, Perry DJ, Poudel P, Schulman S, Schulze H, Stephens JC, Furie B, Robinson PN, van Geet C, Rendon A, Gomez K, Laffan MA, Lambert MP, Nurden P, Ouwehand WH, Richardson S, Mumford AD, Freson K (2015) Human phenotype ontology annotation and cluster analysis to unravel genetic defects in 707 cases with unexplained bleeding and platelet disorders. Genome Med 7(1):36

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Williams MS, Weiss EJ, Sabatine MS, Simon DI, Bahou WF, Becker LC, Parise LV, Dauerman HL, French PA, Smyth SS, Becker RC (2010) Genetic regulation of platelet receptor expression and function: application in clinical practice and drug development. Arterioscler Thromb Vasc Biol 30(12):2372–2384

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wray NR, Pergadia ML, Blackwood DH, Penninx BW, Gordon SD, Nyholt DR, Ripke S, MacIntyre DJ, McGhee KA, Maclean AW, Smit JH, Hottenga JJ, Willemsen G, Middeldorp CM, de Geus EJ, Lewis CM, McGuffin P, Hickie IB, van den Oord EJ, Liu JZ, Macgregor S, McEvoy BP, Byrne EM, Medland SE, Statham DJ, Henders AK, Heath AC, Montgomery GW, Martin NG, Boomsma DI, Madden PA, Sullivan PF (2012) Genome-wide association study of major depressive disorder: new results, meta-analysis, and lessons learned. Mol Psychiatry 17(1):36–48

    Article  CAS  PubMed  Google Scholar 

  • Ye Z, Liu EH, Higgins JP, Keavney BD, Lowe GD, Collins R, Danesh J (2006) Seven haemostatic gene polymorphisms in coronary disease: meta-analysis of 66,155 cases and 91,307 controls. Lancet 367(9511):651–658

    Article  CAS  PubMed  Google Scholar 

  • Zanger UM, Schwab M (2013) Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol Ther 138(1):103–141

    Article  CAS  PubMed  Google Scholar 

  • Zanger UM, Klein K, Thomas M, Rieger JK, Tremmel R, Kandel BA, Klein M, Magdy T (2014) Genetics, epigenetics, and regulation of drug-metabolizing cytochrome p450 enzymes. Clin Pharmacol Ther 95(3):258–261

    Article  CAS  PubMed  Google Scholar 

  • Zhang MY, Churpek JE, Keel SB, Walsh T, Lee MK, Loeb KR, Gulsuner S, Pritchard CC, Sanchez-Bonilla M, Delrow JJ, Basom RS (2015) Germline ETV6 mutations in familial thrombocytopenia and hematologic malignancy. Nat Genet 47(2):180–185

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou D, Andersson TB, Grimm SW (2011) In vitro evaluation of potential drug-drug interactions with ticagrelor: cytochrome P450 reaction phenotyping, inhibition, induction, and differential kinetics. Drug Metab Dispos 39(4):703–710

    Article  CAS  PubMed  Google Scholar 

  • Ziegelstein RC, Parakh K, Sakhuja A, Bhat U (2009) Platelet function in patients with major depression. Intern Med J 39(1):38–43

    Article  CAS  PubMed  Google Scholar 

  • Zuern CS, Schwab M, Gawaz M, Geisler T (2010) Platelet pharmacogenomics. J Thromb Haemost 8(6):1147–1158

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by grants from the National Institutes of Health (HL 091939), NIH/NHLBI DNA Resequencing and Genotyping Service (Subcontract G175), the New York State Stem Cell Foundation (C026716), and the Burroughs Wellcome Fund.

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  1. Department of Medicine, Stony Brook University, Stony Brook, NY, 11794-8151, USA

    Zongdong Li Ph.D., Dmitri V. Gnatenko & Wadie F. Bahou

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  1. Zongdong Li Ph.D.
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  2. Dmitri V. Gnatenko
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  3. Wadie F. Bahou
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Correspondence to Zongdong Li Ph.D. .

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  1. Department of Medicine, Section of Internal and Cardiovascular Medicine, University of Perugia , Perugia, Italy

    Paolo Gresele

  2. Houston Methodist Hospital , Houston, Texas, USA

    Neal S. Kleiman

  3. Bloodworks Northwest, University of Washington , Seattle, Washington, USA

    José A. Lopez

  4. Sackler Inst of Pulmonary Pharmacol, King’s College London, London, United Kingdom

    Clive P. Page

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Li, Z., Gnatenko, D.V., Bahou, W.F. (2017). Platelet Genomics. In: Gresele, P., Kleiman, N., Lopez, J., Page, C. (eds) Platelets in Thrombotic and Non-Thrombotic Disorders. Springer, Cham. https://doi.org/10.1007/978-3-319-47462-5_16

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