Polygenic Hyperlipidemias and Coronary Artery Disease Risk

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http://hdl.handle.net/10138/314469

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FinnGen Project , Ripatti , P , Rämö , J T , Mars , N J , Fu , Y , Lin , J , Söderlund , S , Benner , C , Surakka , I , Kiiskinen , T , Havulinna , A S , Palta , P , Freimer , N B , Widén , E , Salomaa , V , Tukiainen , T , Pirinen , M , Palotie , A , Taskinen , M-R & Ripatti , S 2020 , ' Polygenic Hyperlipidemias and Coronary Artery Disease Risk ' , Circulation-Genomic and precision medicine , vol. 13 , no. 2 , pp. 59-65 . https://doi.org/10.1161/CIRCGEN.119.002725

Title: Polygenic Hyperlipidemias and Coronary Artery Disease Risk
Author: FinnGen Project; Ripatti, Pietari; Rämö, Joel T.; Mars, Nina J.; Fu, Yu; Lin, Jake; Söderlund, Sanni; Benner, Christian; Surakka, Ida; Kiiskinen, Tuomo; Havulinna, Aki S.; Palta, Priit; Freimer, Nelson B.; Widén, Elisabeth; Salomaa, Veikko; Tukiainen, Taru; Pirinen, Matti; Palotie, Aarno; Taskinen, Marja-Riitta; Ripatti, Samuli
Contributor: University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Genomics of Sex Differences
University of Helsinki, Complex Disease Genetics
University of Helsinki, Clinicum
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Complex Disease Genetics
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Centre of Excellence in Complex Disease Genetics
University of Helsinki, Genomics of Sex Differences
University of Helsinki, Centre of Excellence in Complex Disease Genetics
University of Helsinki, Centre of Excellence in Complex Disease Genetics
University of Helsinki, HUS Heart and Lung Center
University of Helsinki, Institute for Molecular Medicine Finland
Date: 2020-04
Language: eng
Number of pages: 7
Belongs to series: Circulation-Genomic and precision medicine
ISSN: 2574-8300
URI: http://hdl.handle.net/10138/314469
Abstract: Background: 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. Methods: We derived polygenic risk scores (PRSs) with approximate to 6M variants separately for LDL-C and TG with weights from a UK Biobank-based genome-wide association study with approximate to 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). Results: 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 1.36 (95% CI, 1.24-1.49) for the LDL-C PRS and 1.31 (95% CI, 1.19-1.43) for the TG PRS. These estimates were only slightly attenuated when adjusting for a CAD PRS (odds ratio, 1.26 [95% CI, 1.16-1.38] for LDL-C and 1.24 [95% CI, 1.13-1.36] for TG PRS). Conclusions: The CAD risk associated with a high polygenic load for lipid-increasing variants was proportional to their impact on lipid levels and partially overlapping with a CAD PRS. In contrast with a PRS for CAD, the lipid PRSs point to known and directly modifiable risk factors providing additional guidance for clinical translation.
Subject: 3111 Biomedicine
1184 Genetics, developmental biology, physiology
3121 General medicine, internal medicine and other clinical medicine
coronary artery disease
humans
hypercholesterolemia
hypertriglyceridemia
risk factors
DENSITY-LIPOPROTEIN CHOLESTEROL
FAMILIAL HYPERCHOLESTEROLEMIA
TRIGLYCERIDES
MUTATIONS
PLASMA
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