Polygenic Hyperlipidemias and Coronary Artery Disease Risk

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dc.contributor.author FinnGen Project
dc.contributor.author Ripatti, Pietari
dc.contributor.author Rämö, Joel T.
dc.contributor.author Mars, Nina J.
dc.contributor.author Fu, Yu
dc.contributor.author Lin, Jake
dc.contributor.author Söderlund, Sanni
dc.contributor.author Benner, Christian
dc.contributor.author Surakka, Ida
dc.contributor.author Kiiskinen, Tuomo
dc.contributor.author Havulinna, Aki S.
dc.contributor.author Palta, Priit
dc.contributor.author Freimer, Nelson B.
dc.contributor.author Widén, Elisabeth
dc.contributor.author Salomaa, Veikko
dc.contributor.author Tukiainen, Taru
dc.contributor.author Pirinen, Matti
dc.contributor.author Palotie, Aarno
dc.contributor.author Taskinen, Marja-Riitta
dc.contributor.author Ripatti, Samuli
dc.date.accessioned 2020-04-28T14:15:01Z
dc.date.available 2020-04-28T14:15:01Z
dc.date.issued 2020-04
dc.identifier.citation 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
dc.identifier.other PURE: 136018720
dc.identifier.other PURE UUID: 861770d4-e1cb-477f-a8e8-c2db8090415a
dc.identifier.other ORCID: /0000-0002-1664-1350/work/73243016
dc.identifier.other ORCID: /0000-0001-9320-7008/work/73243527
dc.identifier.other ORCID: /0000-0002-6429-5149/work/73243823
dc.identifier.other ORCID: /0000-0003-2520-2189/work/73244606
dc.identifier.other ORCID: /0000-0001-9928-1663/work/73244645
dc.identifier.other WOS: 000529978000004
dc.identifier.other ORCID: /0000-0002-6229-3588/work/90757080
dc.identifier.other ORCID: /0000-0002-2527-5874/work/97266643
dc.identifier.uri http://hdl.handle.net/10138/314469
dc.description.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. en
dc.format.extent 7
dc.language.iso eng
dc.relation.ispartof Circulation-Genomic and precision medicine
dc.rights cc_by
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject 3111 Biomedicine
dc.subject 1184 Genetics, developmental biology, physiology
dc.subject 3121 General medicine, internal medicine and other clinical medicine
dc.subject coronary artery disease
dc.subject humans
dc.subject hypercholesterolemia
dc.subject hypertriglyceridemia
dc.subject risk factors
dc.subject DENSITY-LIPOPROTEIN CHOLESTEROL
dc.subject FAMILIAL HYPERCHOLESTEROLEMIA
dc.subject TRIGLYCERIDES
dc.subject MUTATIONS
dc.subject PLASMA
dc.title Polygenic Hyperlipidemias and Coronary Artery Disease Risk en
dc.type Article
dc.contributor.organization Institute for Molecular Medicine Finland
dc.contributor.organization Samuli Olli Ripatti / Principal Investigator
dc.contributor.organization Complex Disease Genetics
dc.contributor.organization Helsinki Institute of Life Science HiLIFE
dc.contributor.organization University of Helsinki
dc.contributor.organization Genomics of Neurological and Neuropsychiatric Disorders
dc.contributor.organization Genomics of Sex Differences
dc.contributor.organization Statistical and population genetics
dc.contributor.organization Clinicum
dc.contributor.organization HUS Internal Medicine and Rehabilitation
dc.contributor.organization Research Programs Unit
dc.contributor.organization CAMM - Research Program for Clinical and Molecular Metabolism
dc.contributor.organization Helsinki University Hospital Area
dc.contributor.organization Centre of Excellence in Complex Disease Genetics
dc.contributor.organization Elisabeth Ingrid Maria Widen / Principal Investigator
dc.contributor.organization Genomic Discoveries and Clinical Translation
dc.contributor.organization Department of Mathematics and Statistics
dc.contributor.organization Biostatistics Helsinki
dc.contributor.organization Department of Public Health
dc.contributor.organization Faculty of Medicine
dc.contributor.organization Aarno Palotie / Principal Investigator
dc.contributor.organization HUS Heart and Lung Center
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.1161/CIRCGEN.119.002725
dc.relation.issn 2574-8300
dc.rights.accesslevel openAccess
dc.type.version publishedVersion
dc.relation.funder Helsingin yliopisto
dc.relation.grantnumber

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