Evolution of Hemostasis Genetics: From Monogenic Disorders to Complex Traits

Researchers at the Institute for Cancer Research and Treatment (IRCCS) Neuromedicine have published a comprehensive review of the advancements in hemostasis genetics over the past five decades. The study highlights the transition from understanding rare Mendelian disorders to exploring complex traits influencing cardiovascular disease risk. By analyzing the historical development of genetic research in hemostasis and thrombosis, the researchers emphasize key methodological breakthroughs and their impact on cardiovascular risk assessment. The review also emphasizes the importance of integrating genetics with emerging technologies to move closer to personalized prevention and therapeutic interventions in thrombotic diseases.

Key Takeaways:

• The study details the evolution of hemostasis genetics from monogenic disorders to complex traits over the past five decades, highlighting key methodological breakthroughs and their impact on cardiovascular risk assessment.
• Research has shifted from studying rare Mendelian disorders to exploring complex traits influencing cardiovascular disease risk, demonstrating the importance of genetics in understanding thrombotic diseases.
• The completion of the Human Genome Project in 2003 enabled genome-wide association studies, identifying novel loci involved in hemostasis and thrombosis and paving the way for personalized treatment strategies.
• Gene-gene and gene-environment interactions, as well as large multicenter studies, have improved the reproducibility of findings, leading to a better understanding of the complex genetic networks involved in hemostasis and thrombosis.
• Mendelian randomization studies have provided compelling evidence of causal relationships between hemostatic factors and cardiovascular outcomes, further supporting the role of genetics in cardiovascular disease.
• Machine learning and artificial intelligence approaches have begun to uncover complex genetic networks, offering new perspectives in precision medicine and personalized prevention and therapeutic interventions in thrombotic diseases.
• The study emphasizes the importance of integrating genetics with emerging technologies to improve cardiovascular risk assessment and treatment strategies.

Statistics:

• Over the past five decades, research has transitioned from studying rare Mendelian disorders to exploring complex traits influencing cardiovascular disease risk.
• The completion of the Human Genome Project in 2003 enabled genome-wide association studies, identifying novel loci involved in hemostasis and thrombosis.
• Polygenic risk scores, integrating the cumulative effect of numerous variants, have refined individual risk prediction, with advances in pharmacogenomics demonstrating how genetic polymorphisms modulate responses to antithrombotic therapies.

Sources:

• The evolution of hemostasis genetics: from monogenic disorders to complex traits. A historical perspective. (2025,4(2)).
• Institute for Cancer Research and Treatment (IRCCS) Neuromedicine, Research Unit of Epidemiology and Prevention.
• https://doi-org.sdpl.idm.oclc.org/10.4081/btvb.2025.184.