Inherited dysfunctional nitric oxide signaling and the pathobiology of atherothrombotic disease

Abstract

Using genome-wide association studies and exome sequencing, large numbers of genetic loci conferring an increased risk of a wide variety of diseases have been identified, revealing new genes and pathways not previously suspected to be relevant in pathobiology. For common complex diseases such as atherosclerosis, hypertension, diabetes, and heart failure, single-nucleotide polymorphisms (SNPs) associated with increased risk typically have small effect sizes and appear to only account for a small fraction of the genetic risk. These data suggest that the majority of patients likely to develop common diseases such as atherosclerosis are unlikely to be identified by currently defined SNPs. A recent article in Nature diverges from the population-wide approach to elucidate select variants by studying a family with excessive cardiovascular disease in younger adults and identifies mutations in two functionally related genes that may be linked to atherothrombotic disease.