Recent developments in cardiovascular genetics and genomics.

Abstract

The rapid pace of genetic and genomic discoveries in cardiovascular medicine remains unabated. During the past few years, several new causal genes and susceptibility variants for several cardiovascular disease have been identified.1–7 Likewise, genomic and epigenetic discoveries, encompassing noncoding RNAs, DNA methylation, and covalent histone modifications, have shed significant light onto the mechanisms that regulate expression of the cardiovascular phenotypes.5,8–13 Although the main impact of the genetic and genomic discoveries has been in elucidation of the molecular pathogenesis of cardiovascular diseases, recent findings, particularly in single gene discoveries, are also clinically impactful and are becoming increasingly incorporated into the practice of cardiovascular medicine.14–24 In addition, these discoveries have paved the way for genetic-based interventions and gene therapy.25–28 The discoveries have also enabled generation and mechanistic characterization of induced pluripotent stem cell models of genetic cardiovascular diseases.29–35 This progress has been driven in part by the technological advances, most notably the massively parallel nucleic acid sequencing techniques, which have enabled sequencing of the entire human exome, if not the genome, and the whole transcriptome of an individual within a reasonable cost.36,37 The ability to decode an individual exome has also posed a daunting challenge to clinicians and researchers as well as the patients in an accurate identification of the causal or risk variants from the myriad of variants that are present in each exome and in the population.38–40 The plethora of variants in each exome and genome underscores the necessity of incorporating family information in increasing the use of the genetic data and garnering clinically robust and meaningful genetic information. Approaches to the elucidation of genetic causes of cardiovascular diseases have evolved along with the technological advances. Conventional …