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Polygenic influences on dyslipidemias

Dron, Jacqueline S., Hegele, Robert A.·2018·Current Opinion in Lipidology
DOI 10.1097/mol.0000000000000482
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Abstract

Purpose of review: Rare large-effect genetic variants underlie monogenic dyslipidemias, whereas common small-effect genetic variants – single nucleotide polymorphisms (SNPs) – have modest influences on lipid traits. Over the past decade, these small-effect SNPs have been shown to cumulatively exert consistent effects on lipid phenotypes under a polygenic framework, which is the focus of this review. Recent findings: Several groups have reported polygenic risk scores assembled from lipid-associated SNPs, and have applied them to their respective phenotypes. For lipid traits in the normal population distribution, polygenic effects quantified by a score that integrates several common polymorphisms account for about 20–30% of genetic variation. Among individuals at the extremes of the distribution, that is, those with clinical dyslipidemia, the polygenic component includes both rare variants with large effects and common polymorphisms: depending on the trait, 20–50% of susceptibility can be accounted for by this assortment of genetic variants. Summary: Accounting for polygenic effects increases the numbers of dyslipidemic individuals who can be explained genetically, but a substantial proportion of susceptibility remains unexplained. Whether documenting the polygenic basis of dyslipidemia will affect outcomes in clinical trials or prospective observational studies remains to be determined.

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  • Only an estimated 20-30% of the heritability of lipid traits is currently explained.

    “Moreover, only an estimated 20–30% of the heritability of lipid traits is currently explained[12].”

    From Genome-scale CRISPR screening for modifiers of cellular LDL uptake (2021) · cites this paper as [12]

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Metadata

Authors
Dron, J. S., & Hegele, R. A.
Affiliations
Department of Biochemistry
Venue
Current Opinion in Lipidology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2018-04
Volume
29
Issue
2
Pages
133-143
ISSN
  • 0957-9672
  • 1473-6535
DOI
10.1097/mol.0000000000000482
Cited by
59
References
7
Language
en

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