High Polygenic Snp Scores Do Not Exclude Monogenic Familial Hypercholesterolaemia

Background and Aims: Mutations in the LDLR, APOB and PCSK9 genes affecting the LDL-receptor pathway are known to cause autosomal dominant Familial Hypercholesterolaemia (FH). In approximately 20% of probands with a definite clinical diagnosis of FH no mutations are detected suggesting that there are FH causing mutations located in other genes. However it is proposed that polygenic SNP scores above the median in mutation negative patients infer a low likelihood of monogenic FH.