Genetics of Cardiovascular Disease

Fifty years ago, cardiovascular genetics simply did not exist. Genetics was a nascent field of basic research, with little apparent relevance to cardiovascular science or any other medical subspecialty. Today, cardiovascular genetics is a discipline that fully integrates high-technology laboratory investigation and clinical medicine. From this hybrid have emerged discoveries that have precisely identified the cause of heretofore “idiopathic” disorders, provided fundamental insights into disease processes, and delineated subtypes in well-defined pathologies. Insights from these discoveries uproot traditional anatomic classifications of disease and integrate cell physiology and molecular biochemistry into the study of pathology. For researchers, practitioners, and patients alike, cardiovascular genetics is having a growing impact on the definition and diagnosis of disease, the explanation of prognosis, and the expansion of treatments. While appreciating the progress that cardiovascular genetics has achieved, one must be mindful of antecedent and seminal discoveries in the broader field of genetics that enabled the birth and growth of the molecular era. By the mid 1900s, Mendel’s theory of inheritance was proven, the segregation and assortment of chromosomes during meiosis was recognized, the linear arrangement of genes on chromosomes was appreciated, and recombination frequency was accepted as an accurate assessment for the distances between genes.1 Even the potential for assigning genetic traits to specific chromosomes through the study of human inheritance was appreciated: familial transmission of color blindness and hemophilia was correctly interpreted to indicate genes encoded on the X chromosome.2 3 Any review of the critical developments that fostered the birth of cardiovascular genetics must acknowledge the enormous contributions made by clinicians, patients, and families. For advances in genetics to become relevant to clinical cardiology, the heritable nature of cardiovascular disease needed to be recognized. This recognition was gained through case reports, descriptions of the familial aggregation of diseases, and epidemiological studies, …