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 organization: | Institute for Molecular Medicine Finland Samuli Olli Ripatti / Principal Investigator Complex Disease Genetics Helsinki Institute of Life Science HiLIFE University of Helsinki Genomics of Neurological and Neuropsychiatric Disorders Genomics of Sex Differences Statistical and population genetics Clinicum HUS Internal Medicine and Rehabilitation Research Programs Unit CAMM - Research Program for Clinical and Molecular Metabolism Helsinki University Hospital Area Centre of Excellence in Complex Disease Genetics Elisabeth Ingrid Maria Widen / Principal Investigator Genomic Discoveries and Clinical Translation Department of Mathematics and Statistics Biostatistics Helsinki Department of Public Health Faculty of Medicine Aarno Palotie / Principal Investigator HUS Heart and Lung Center |
Date: | 2020-04 |
Language: | eng |
Number of pages: | 7 |
Belongs to series: | Circulation-Genomic and precision medicine |
ISSN: | 2574-8300 |
DOI: | https://doi.org/10.1161/CIRCGEN.119.002725 |
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 |
Peer reviewed: | Yes |
Rights: | cc_by |
Usage restriction: | openAccess |
Self-archived version: | publishedVersion |
Funder: | Helsingin yliopisto |
Grant number: |
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