Evidence mapPaperPMID 40801957Full record

ReviewCurrent atherosclerosis reports2025

Polygenic Modulation of Monogenic Diseases: Familial Hypercholesterolemia as the Exemplar.

Liam R Brunham

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Review in Current atherosclerosis reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

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5 · Who and what money

Authors and funding

1 author.

Liam R BrunhamCentre for Heart Lung Innovation, University of British Columbia and St. Paul's Hospital, 16 - 1081 Burrard Street, Vancouver, BC, V7L2B3, Canada. Liam.brunham@ubc.ca.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purpose of reviewHeterozygous Familial Hypercholesterolemia (HeFH) is among the most common genetic conditions worldwide that affects ~ 1 in 300 individuals. HeFH is characterized by increased levels of low-density lipoprotein cholesterol (LDL-C) and increased risk of coronary artery disease (CAD), but there is a wide spectrum of severity within the HeFH population. This variability in expression is incompletely explained by known risk factors. The purpose of this review is to discuss recent studies that have examined how polygenic risk can modulate the phenotypic expression of HeFH. RECENT

findingsOver the past several years, polygenic risk scores (PRS) that summarize information about many genetic variants that influence various traits have been developed. This includes polygenic risk scores for levels of LDL-C and other lipid fractions, CAD, and various other cardio-metabolic traits. In some individuals with a clinical phenotype compatible with HeFH but in whom a pathogenic variant is not present, an elevated PRS for LDL-C may explain the hypercholesterolemia. Among individuals with monogenic HeFH, an elevated PRS for LDL-C or CAD can further exacerbate the clinical phenotype and increase the risk of cardiovascular events. Conversely, a low PRS for these traits can mask the presentation of HeFH by decreasing the clinical severity and thus lead to incomplete phenotypic penetrance of a pathogenic HeFH-causing variant. Although HeFH is a prototypical monogenic condition, recent studies have revealed how the genomic background, as reflected by PRSs, can further modulate the clinical phenotype up or down in severity, thus adding a previously unrecognized level of complexity to monogenic disease. Having identified PRSs that can alter the clinical trajectory of HeFH, the next challenge for the field will be to implement PRS testing into clinical practice to allow clinicians to tailor risk prediction and treatment approaches based on each individual's unique complement of genetic factors.

Indexed as

Hyperlipoproteinemia Type IIMultifactorial InheritanceCholesterol, LDLCoronary Artery DiseaseGenetic Predisposition to DiseaseHumansPhenotypeRisk FactorsCholesterol, LDLAtherosclerosisCholesterolFamilial hypercholesterolemiaGeneticsLipidsPolygenic risk

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.