Overview of possible consequences of CAD risk variants. Variant types (top right): about 95% of all ∼18 500 variants in LD with 393 proxy CAD-associated variants (r² > 0.6) are in the non-coding region. About 60% of all CAD-associated variants in LD have regulatory potential as they either overlap with CREs from ENCODE/SCREEN,²⁵ with VEP enhancer elements (Ensembl Variant Effect Predictor¹⁸) rank high in the RegulomeDB (ranking ≤ 2a or probability score > 0.8),²⁶ or have a high score in other data sets (ABC score > 0.04 or Open Targets Genetics score > 0.7). Variant consequences (top right): most variants are in introns and about 56.7% of these intronic variants may show regulatory potential by altering enhancer activity or by impacting mRNA splicing (splice variants). Variant consequences are from the Ensembl VEP.¹⁸ Variant mechanisms (bottom left): CAD risk variant can affect gene expression (transcription or translation) as well as protein function. Examples of molecular mechanisms of genes in grey boxes are described in Table 2. CAD risk factors (bottom right): the combination of risk variants can ultimately impact CAD causing molecular risk factors such as LDL cholesterol, which are often associated with clinical risk factors such as obesity. The complete list of causal traits, biomarkers, and diseases derived from Mendelian randomization studies can be found in a review article by Chen and Schunkert.²⁷