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SNPs and coronary angiography: can vascular biology be done from angiograms?

David C. Crossman
DOI: http://dx.doi.org/10.1093/eurheartj/ehq333 2977-2979 First published online: 23 September 2010

This editorial refers to ‘The chromosome 9p21 risk locus is associated with angiographic severity and progression of coronary artery disease’, by R.S. Patel et al., on page 3017

Coronary artery disease (CAD) is well known to be, to some degree, heritable. A family history of premature CAD is an established risk factor, and studies in monozygotic twins indicate that this effect is genetic rather than from a shared environment.1 These well established truths have been the driving force behind genetic studies of patients with CAD. An initial wave of studies ∼15 years ago examining informative mutations in candidate genes produced a large collection of underpowered studies that were characterized by lack of reproducibility when tested in larger cohorts, with the exception of variants in the apo ε gene.2 The next wave of genetic studies consisted of family-based, linkage studies usually of prematurely affected individuals. These repeated the experience of lack of reproducibility between studies and introduced a new problem, that of identified areas of the genome thought to be causative having no identifiable gene to which a function could be ascribed. Linkage studies did, however, indicate that the task of identifying genetic markers/causes of CAD was going to be tough, with many genes having small additive or interactive effects. The lack of power in the linkage studies, and their vulnerability to disease misclassification, prompted a return to association-based structures but now with herculean numbers of patients and unbiased screening of the whole genome using increasingly dense maps of identified genetic variants [single nucleotide polymorphisms (SNPs)] scattered across the human genome. These have led to the genome-wide association studies (GWAS), which have led to new and potentially very exciting data.

Why so much excitement? First, there has now been replication between studies and, secondly, a handful …