The Future of Genetics and Genomics

In this forward-facing review, we briefly summarize what we see as the state of modern cardiovascular genetics and genomics before outlining some of the key areas in which we believe there is a need for investment if we are to realize the full clinical potential of the field. There is clearly substantial overlap with the field of precision medicine, yet it may be in understanding where genetics and genomics currently fall short that we will identify how precision medicine might move forward.1,2 The recognition over the last decade that genetics or genomics alone is unlikely to offer the predictive utility necessary for precision medicine is matched by our dependence on genetics and genomics for much of the mechanistic insight necessary to achieve precision diagnostics or precision therapeutics.2 The overarching strategies we discuss emphasize that the future of cardiovascular genetics and genomics is inextricably linked with those of every other field of medicine. We must move beyond the silos of traditional organ-based disease if we are to realize fully the need for generalizable biological rules that constitute the truly mechanistic medicine or molecular medicine first envisaged >40 years ago.3The cardiovascular arena has been a focus of much work on the practical application of genetics. Given the potential for coincident presentation and demise in sudden death and the availability of the implantable defibrillator (a mechanism-agnostic preventive therapy), cardiovascular medicine has been focused on the predictive utility of genetics for some time.4 The long tradition of physiological measurements and classic epidemiology in cardiovascular research has facilitated large genotype-phenotype correlation studies.5,6 Cardiovascular research has also had to tackle truly complex paroxysmal phenotypes such as arrhythmias that have challenged our ability to resolve traits into their constituent components.7Large kindreds, with what in retrospect …