Recent Advances in the Genetics of Atherothrombotic Disease and Its Determinants

Over the past 2 years, the pace of scientific discovery in human genetics related to atherothrombotic disease and vascular biology has been rapid, with no shortage of innovative articles published in ATVB. Several studies have identified novel loci by genetic association approaches, whereas others focused on validating genome-wide association study (GWAS) data functionally. Strides were also made with micro-RNAs (miRNAs) and their use as biomarkers and therapeutic targets in disease. Furthermore, molecular and mechanistic bases of certain genetic conditions, including dyslipidemias, were characterized. Here, we review genetic-themed articles published in ATVB since 2015, which highlight rapid advances in the field.A popular type of study in human genetics is the association study, which classically is performed in 1 of 2 forms.1 In the first, a quantitative phenotypic feature is measured in a population sample, genotypic strata are created from alleles of a common DNA variant, and differences between genotypic classes are tested statistically. In the second, cases with a discrete trait or disorder are matched with controls who are free of the trait. Both groups are genotyped for a common DNA variant, and differences in allele or genotype frequencies between cases and controls are evaluated statistically. Both forms of association studies can be performed millions of times with microarrays that genotype single nucleotide polymorphisms (SNPs) from across the human genome, with adjustments for multiple testing; the extreme case is GWAS. Often, when results are reported, there is no direct experimental testing of biological impact of the associated alleles. For instance, in 812 participants of the 15-year Bruneck study, a noncoding DNA microsatellite polymorphism in the promoter region of the HMOX1 gene, encoding heme oxidase-1 was associated with increased carotid atherosclerosis and a trend to higher levels of oxidized phospholipids; however, …