Plasma levels of lipids and lipoproteins are governed by interactions between genetic and non-genetic factors (1). The genetic component of dyslipidaemias can be monogenic or polygenic, or both (1). Monogenic dyslipidaemias are caused by rare genetic variants with large, highly penetrant effects and their inheritance in families follows Mendelian rules (2). In these conditions, of which familial hypercholesterolaemia (FH) (3) and familial chylomicronaemia syndrome (FCS) (4) are familiar examples, genetic testing can help confirm the diagnosis, which in turn can affect management and screening of family members (Table 1) (5), ∗6), 7)). In contrast, polygenic dyslipidaemias result from the concurrent contributions of multiple common DNA variants, i.e., single nucleotide polymorphisms (SNPs), whose additive impact on the lipoprotein profile can approximate that of a rare monogenic variant of large-effect (8), 8)a, 8)b, ∗9), 10), 11), 12)). Inheritance of polygenic dyslipidaemia does not follow Mendelian rules (9). The influence of common SNPs is quantified using a polygenic score (13), 14), 15), ∗16)). Most patients with severe hypertriglyceridaemia have polygenic susceptibility and not a discrete monogenic cause (9).

In this review, we focus on monogenic dyslipidaemias, particularly FH, in which genetic testing offers net clinical benefits; some clinical algorithms for FH now include genetic testing (17). In contrast, genetic testing for polygenic dyslipidaemia, principally hypertriglyceridaemia, is not recommended; further research will determine the utility of polygenic scores in clinical practice (13), 14), 15), ∗16)). Here we review potential benefits and pitfalls genetic testing as applied to dyslipidaemia.