Role of Genetics in Early-Onset Cardiovascular Disease

Abstract

Genetics increasingly comes to the front with early-onset cardiovascular disease (CVD) since researchers investigate the complex interplay of hereditary factors that promote an early manifestation of the disease. CVD is one of the most general causes of morbidity and mortality worldwide, presenting unique challenges when it arises in younger populations many times due to genetic predispositions. The various etiologies in the pathogenesis of early-onset CVD involve genetic factors, including the monogenic disorders of familial hypercholesterolemia (FH) and hypertrophic cardiomyopathy (HCM) of these diseases showing the simple Mendelian patterns of inheritance. These may be mediated through gene variations, including Low-Density Lipoprotein Receptor (LDLR), Apolipoprotein B (APOB), Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9), and Myosin Heavy Chain 7 (MYH7). Disrupted lipid metabolism, myocardial function, or vascular integrity due to mutations could lead to adverse clinical consequences. Moreover, polygenic risk score (PRS) has now become helpful in identifying individuals who are at elevated risk due to the cumulative effect of several genetic variants. Knowledge about gene-environment interactions, epigenetic influences, and complex regulatory networks contributes to understanding the importance of genetic contributions to early-onset CVD. However, the genetic variation is population-specific and underlines the need for research inclusive of diverse genetic backgrounds in developing more inclusive and effective predictive models. Whole genome and exome sequencing have revolutionized early detection, making personalized treatment plans possible, including targeted therapeutic interventions like PCSK9 inhibitors. On the other hand, such scientific progress also provides a lot of ethical challenges, such as utilizing personal data, informed consent, and equal access to genetic services. This review summarizes the genetic basis underlying early-onset CVD, with detailed discussions of monogenic and polygenic contributions, important genetic pathways, and emerging advances in genetic testing and personalized medicine approaches. By highlighting the integration of genetic insights with preventive and therapeutic strategies, this review aims to bring into focus the use of genetic insight in the betterment of outcomes in patients and inform future research in cardiovascular genetics.

Keywords: early-onset cardiovascular disease; genetic predisposition; genetic testing and personalized medicine; monogenic disorders; polygenic risk score.