Polygenic Hyperlipidemias and Coronary Artery Disease Risk.

Circulation. Genomic and Precision Medicine
Pietari RipattiFinnGen†

Abstract

Hyperlipidemia is a highly heritable risk factor for coronary artery disease (CAD). While monogenic familial hypercholesterolemia associates with severely increased CAD risk, it remains less clear to what extent a high polygenic load of a large number of LDL (low-density lipoprotein) cholesterol (LDL-C) or triglyceride (TG)-increasing variants associates with increased CAD risk. We derived polygenic risk scores (PRSs) with ≈6M variants separately for LDL-C and TG with weights from a UK Biobank-based genome-wide association study with ≈324K samples. We evaluated the impact of polygenic hypercholesterolemia and hypertriglyceridemia to lipid levels in 27 039 individuals from the National FINRISK Study (FINRISK) cohort and to CAD risk in 135 638 individuals (13 753 CAD cases) from the FinnGen project (FinnGen). In FINRISK, median LDL-C was 3.39 (95% CI, 3.38-3.40) mmol/L, and it ranged from 2.87 (95% CI, 2.82-2.94) to 3.78 (95% CI, 3.71-3.83) mmol/L between the lowest and highest 5% of the LDL-C PRS distribution. Median TG was 1.19 (95% CI, 1.18-1.20) mmol/L, ranging from 0.97 (95% CI, 0.94-1.00) to 1.55 (95% CI, 1.48-1.61) mmol/L with the TG PRS. In FinnGen, comparing the highest 5% of the PRS to the lowest 95%, CAD odds ratio was...Continue Reading

References

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Citations

Jul 6, 2020·Human Molecular Genetics·Tatiane YanesShelly Cummings
Dec 12, 2020·Journal of Clinical Lipidology·Praneet K GillRobert A Hegele
Feb 11, 2021·International Journal of Molecular Sciences·Leonor Jacobo-AlbaveraTeresa Villarreal-Molina
Jan 5, 2021·Current Opinion in Lipidology·Mark Trinder, Liam R Brunham
Feb 5, 2021·Current Opinion in Lipidology·Hannah WandShoa L Clarke
Apr 6, 2021·Current Opinion in Cardiology·Praneet K GillRobert A Hegele
Oct 29, 2020·BMC Medicine·Haoxiang ChengInga Peter
May 11, 2021·Journal of Human Genetics·Akihiro NomuraMasa-Aki Kawashiri
Aug 20, 2021·Arteriosclerosis, Thrombosis, and Vascular Biology·Eythór BjörnssonKári Stefánsson

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Methods Mentioned

BETA
genotyping

Software Mentioned

ePerMed

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