The evolution of hemostasis genetics: from monogenic disorders to complex traits. A historical perspective

The genetics of hemostasis factors has evolved over the past five decades, transitioning from the study of rare Mendelian disorders to the exploration of complex traits influencing cardiovascular disease risk. Early research focused on single-gene mutations responsible for bleeding disorders. By th...

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Main Author: Augusto Di Castelnuovo
Format: Article
Language:English
Published: PAGEPress Publications 2025-06-01
Series:Bleeding, Thrombosis and Vascular Biology
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Online Access:https://www.btvb.org/btvb/article/view/184
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author Augusto Di Castelnuovo
author_facet Augusto Di Castelnuovo
author_sort Augusto Di Castelnuovo
collection DOAJ
description The genetics of hemostasis factors has evolved over the past five decades, transitioning from the study of rare Mendelian disorders to the exploration of complex traits influencing cardiovascular disease risk. Early research focused on single-gene mutations responsible for bleeding disorders. By the 1990s, candidate gene studies identified associations between common polymorphisms and thrombotic risk. However, inconsistencies across studies highlighted the need for more robust approaches. The completion of the Human Genome Project in 2003 represented a turning point, enabling genome-wide association studies and the identification of novel loci involved in hemostasis and thrombosis. This era also introduced gene-gene and gene-environment interactions, as well as large multicenter studies that improved the reproducibility of findings. Subsequent years saw the development of polygenic risk scores, integrating the cumulative effect of numerous variants to refine individual risk prediction. Advances in pharmacogenomics further demonstrated how genetic polymorphisms modulate responses to antithrombotic therapies, paving the way for personalized treatment strategies. More recently, Mendelian randomization studies have provided compelling evidence of causal relationships between hemostatic factors and cardiovascular outcomes. Simultaneously, machine learning and artificial intelligence approaches have begun to uncover complex genetic networks, offering new perspectives in precision medicine. This review traces the chronological development of genetic research in hemostasis and thrombosis, emphasizing key methodological breakthroughs and their impact on cardiovascular risk assessment. By integrating genetics with emerging technologies, the field moves closer to personalized prevention and therapeutic interventions in thrombotic diseases.
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spelling doaj-art-20f628f64bdb4ecca34a0e9ebfa3df752025-08-20T03:31:26ZengPAGEPress PublicationsBleeding, Thrombosis and Vascular Biology2785-53092025-06-014210.4081/btvb.2025.184The evolution of hemostasis genetics: from monogenic disorders to complex traits. A historical perspectiveAugusto Di Castelnuovo0Research Unit of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli (IS) The genetics of hemostasis factors has evolved over the past five decades, transitioning from the study of rare Mendelian disorders to the exploration of complex traits influencing cardiovascular disease risk. Early research focused on single-gene mutations responsible for bleeding disorders. By the 1990s, candidate gene studies identified associations between common polymorphisms and thrombotic risk. However, inconsistencies across studies highlighted the need for more robust approaches. The completion of the Human Genome Project in 2003 represented a turning point, enabling genome-wide association studies and the identification of novel loci involved in hemostasis and thrombosis. This era also introduced gene-gene and gene-environment interactions, as well as large multicenter studies that improved the reproducibility of findings. Subsequent years saw the development of polygenic risk scores, integrating the cumulative effect of numerous variants to refine individual risk prediction. Advances in pharmacogenomics further demonstrated how genetic polymorphisms modulate responses to antithrombotic therapies, paving the way for personalized treatment strategies. More recently, Mendelian randomization studies have provided compelling evidence of causal relationships between hemostatic factors and cardiovascular outcomes. Simultaneously, machine learning and artificial intelligence approaches have begun to uncover complex genetic networks, offering new perspectives in precision medicine. This review traces the chronological development of genetic research in hemostasis and thrombosis, emphasizing key methodological breakthroughs and their impact on cardiovascular risk assessment. By integrating genetics with emerging technologies, the field moves closer to personalized prevention and therapeutic interventions in thrombotic diseases. https://www.btvb.org/btvb/article/view/184geneticshistoryhemostasis
spellingShingle Augusto Di Castelnuovo
The evolution of hemostasis genetics: from monogenic disorders to complex traits. A historical perspective
Bleeding, Thrombosis and Vascular Biology
genetics
history
hemostasis
title The evolution of hemostasis genetics: from monogenic disorders to complex traits. A historical perspective
title_full The evolution of hemostasis genetics: from monogenic disorders to complex traits. A historical perspective
title_fullStr The evolution of hemostasis genetics: from monogenic disorders to complex traits. A historical perspective
title_full_unstemmed The evolution of hemostasis genetics: from monogenic disorders to complex traits. A historical perspective
title_short The evolution of hemostasis genetics: from monogenic disorders to complex traits. A historical perspective
title_sort evolution of hemostasis genetics from monogenic disorders to complex traits a historical perspective
topic genetics
history
hemostasis
url https://www.btvb.org/btvb/article/view/184
work_keys_str_mv AT augustodicastelnuovo theevolutionofhemostasisgeneticsfrommonogenicdisorderstocomplextraitsahistoricalperspective
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