Table 5.

Top new insights into dyslipidemia from experience with LipidSeq panel

Insight	Reference
About 50% of referred patients thought to have heterozygous FH with LDL cholesterol > 5 mmol/L (> 190 mg/dL) had a likely causative rare variant. This rises to > 90% for patients with LDL cholesterol > 8 mmol/L (> 310 mg/dL).	[44]
About 10% of rare variants causing HeFH are CNVs of the LDLR gene.	[32]
A whole-gene duplication of PCSK9 is a novel, rare cause of HeFH.	[43]
At least 20% of suspected HeFH patients without rare variants have a high LDL cholesterol polygenic SNP score.	[44]
PCSK9 inhibitors are equally effective in patients with either monogenic or polygenic severe hypercholesterolemia.	[49]
Severe hypertriglyceridemia is mostly defined by rare heterozygous variants and a high triglyceride polygenic SNP score.	[45]
The clinical phenotype in monogenic chylomicronemia is essentially identical irrespective of underlying causative genes and variants.	[50]
Hypoalphalipoproteinemia is usually polygenic, comprising both rare heterozygous variants and a high HDL cholesterol polygenic SNP score.	[55]

Abbreviations: CNV copy-number variant, FH familial hypercholesterolemia, HeFH heterozygous familial hypercholesterolemia, LDL low-density lipoprotein, SNP single-nucleotide polymorphism