A signature of platelet reactivity in CBC scattergrams reveals genetic predictors of thrombotic disease risk

Verdier, H., Thomas, P., Batista, J. ORCID: https://orcid.org/0000-0001-5406-6353, Kempster, C. ORCID: https://orcid.org/0000-0001-5721-1050, McKinney, H., Gleadall, N. ORCID: https://orcid.org/0000-0002-1132-1059, Danesh, J., Mumford, A. ORCID: https://orcid.org/0000-0002-5523-511X, Heemskerk, J. W. M. ORCID: https://orcid.org/0000-0002-2848-5121, Ouwehand, W. H. ORCID: https://orcid.org/0000-0002-7744-1790, Downes, K., Astle, W. J. ORCID: https://orcid.org/0000-0001-8866-6672 and Turro, E. ORCID: https://orcid.org/0000-0002-1820-6563 (2023) A signature of platelet reactivity in CBC scattergrams reveals genetic predictors of thrombotic disease risk. Blood, 142 (22). pp. 1895-1908. ISSN 1528-0020 doi: 10.1182/blood.2023021100

Abstract/Summary

Genetic studies of platelet reactivity (PR) phenotypes may identify novel antiplatelet drug targets. However, such studies have been limited by small sample sizes (n < 5000) because of the complexity of measuring PR. We trained a model to predict PR from complete blood count (CBC) scattergrams. A genome-wide association study of this phenotype in 29 806 blood donors identified 21 distinct associations implicating 20 genes, of which 6 have been identified previously. The effect size estimates were significantly correlated with estimates from a study of flow cytometry–measured PR and a study of a phenotype of in vitro thrombus formation. A genetic score of PR built from the 21 variants was associated with the incidence rates of myocardial infarction and pulmonary embolism. Mendelian randomization analyses showed that PR was causally associated with the risks of coronary artery disease, stroke, and venous thromboembolism. Our approach provides a blueprint for using phenotype imputation to study the determinants of hard-to-measure but biologically important hematological traits.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/114307
Identification Number/DOI	10.1182/blood.2023021100
Refereed	Yes
Divisions	Interdisciplinary centres and themes > Institute for Cardiovascular and Metabolic Research (ICMR)
Uncontrolled Keywords	Cell Biology, Hematology, Immunology, Biochemistry
Publisher	American Society of Hematology
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