Coronary artery disease (CAD) develops multifactorially through an interplay of lifestyle, environmental and genetic factors. Smoking, hypertension, hyperlipidemia, obesity and diabetes mellitus are modifiable risk factors for CAD. In addition, both rare mutations and multiple frequently occurring genetic variants can cause CAD, whereby the heritability of CAD is ca. 50%. Genetic diagnostics enable the early identification of affected children and adults and, based on a greatly increased cardiovascular risk, initiation of preventive treatment. In recent years, genome-wide association studies have identified hundreds of significant variants that together greatly increase the risk of CAD. In the general population the many frequently occurring risk alleles in combination with modifiable risk factors result in a widespread genetic predisposition to CAD. Their relevance arises in the context of an integrative risk assessment, whereby the additional genetic risk can be calculated by polygenic risk scores (PRS), which provide a hazard ratio that can be multiplied with the clinically determined risk. This overview article discusses the diagnostic principles of rare and frequent genetic causes of CAD as well as their implications in the precision treatment of the disease.
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