do polygenic risk scores improve cardiovascular risk prediction


Get weekly and/or daily updates delivered to your inbox. Circ Genom Precis Med. pdf icon external icon Moorthie S, et al.

Coronary heart disease genetic risk score predicts cardiovascular disease risk in men, not women. The standard coronary heart disease (CHD) model includes sex, age, 5 principal components, and the binary classifier for low or high risk are based on the pooled risk equations. Independently of the clinical score, the PRS was associated with a ~50% higher risk of AF per SD (HR 1.57; 95% CI 1.54–1.59) and a 2.5-­fold higher risk (HR 2.59; 95% CI 2.47–2.71) when comparing those in the top vs. the bottom third of the PRS. Vanderbilt®, Vanderbilt University Medical Center®, V Oak Leaf Design®, Monroe Carell Jr. Children’s Hospital at Vanderbilt® and Vanderbilt Health® are trademarks of The Vanderbilt University. Conflict of Interest Disclosures: Dr Gupta reported receiving grants from National Institutes of Health (NIH). Incident CHD events occurred in 696 participants (14.4%) and 227 participants (9.5%), respectively, over median follow-up of 15.5 years (interquartile range [IQR], 6.3 years) and 14.2 (IQR, 2.5 years) years.  |  2020:jmedgenet-2019-106763. This is a preview of subscription content, log in to check access. The overall net reclassification improvement is defined as the sum of the net reclassifications for events and nonevents (eg, –0.012 + 0.032 = 0.02). Sarwar N, Butterworth AS, IL6R Genetics Consortium Emerging Risk Factors Collaboration et al. The polygenic risk score did not significantly improve calibration in either cohort. 2010;376:1393–400. PubMed  A Journey through Genetic Architecture and Predisposition of Coronary Artery Disease.

Our mission: To reduce the burden of cardiovascular disease. Abdulrahim JW, Kwee LC, Alenezi F, Sun AY, Baras A, Ajayi TA, Henao R, Holley CL, McGarrah RW, Daubert JP, Truby LK, Vemulapalli S, Wang A, Khouri MG, Shah SH.

Weights were based on an international genome-wide association study.

Epidemiol., 41 … The authors concluded that incorporating genetic information into AF risk prediction tools may help to identify higher risk individuals who may benefit from earlier monitoring and personalised risk-management strategies.

BACKGROUND: Since screening programs identify only a small proportion of the population as eligible for an intervention, genomic prediction of heritable risk factors could decrease the number needing to be screened by removing individuals at low genetic risk. Babb de Villiers C, Kroese M, Moorthie S. Understanding polygenic models, their development and the potential application of polygenic scores in healthcare.

Importance: Polygenic risk scores comprising millions of single-nucleotide polymorphisms (SNPs) could be useful for population-wide coronary heart disease (CHD) screening. The study population included 4847 adults from the ARIC study (mean [SD] age, 62.9 [5.6] years; 56.4% women) and 2390 adults from the MESA cohort (mean [SD] age, 61.8 [9.6] years; 52.2% women). All rights reserved.

Fox KA, Carruthers K, Steg PG, Avezum A, Granger CB, Montalescot G, et al.


Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease. Do Polygenic Risk Scores Improve Patient Selection for Prevention of Coronary Artery Disease?

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A polygenic risk score (PRS) was constructed based on 142 independent genetic variants previously associated with AF in a meta-analysis from the AFGen Consortium.

JAMA. Inouye M, Abraham G, Nelson CP, et al; UK Biobank CardioMetabolic Consortium CHD Working Group. Helgadottir A, Thorleifsson G, Manolescu A, Gretarsdottir S, Blondal T, Jonasdottir A, et al.

This site needs JavaScript to work properly. Hindy G, Aragam KG, Ng K, Chaffin M, Lotta LA, Baras A; Regeneron Genetics Center, Drake I, Orho-Melander M, Melander O, Kathiresan S, Khera AV. NIH

2015;44:682–8. Elliott J, Bodinier B, Bond TA, Chadeau-Hyam M, Evangelou E, Moons KGM, et al. What are polygenic scores and why are they important? Aragam KG, Natarajan P. Polygenic scores to assess atherosclerotic cardiovascular disease risk: clinical perspectives and basic implications. Tags: 58942, Bayesian, linkage-disequilibrium, non-europeans, polygenic risk score, risk prediction.

Algorithms including both traditional risk factors and polygenic risk scores (PRS) can significantly improve prediction of atherosclerotic cardiovascular disease (ASCVD). Improve polygenic risk prediction for non-European populations Jun 1, 2020.


No other disclosures were reported. Genetic risk was computed for each participant by summing the product of the weights and allele dosage across 6 630 149 SNPs. Science. 5823194, © 2020 PHG Foundation

2020;141:624–636. A multilocus genetic risk score for coronary heart disease: case-control and prospective cohort analyses.

2020 Nov;40(11):2738-2746. doi: 10.1161/ATVBAHA.120.314856.  | 

Vanderbilt University Medical Center is committed to principles of equal opportunity and affirmative action.

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology. : 17-05225-EF-1.

Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: an analysis of primary and secondary prevention trials.

Schunkert H, König IR, Kathiresan S, et al; Cardiogenics; CARDIoGRAM Consortium. Cell. Cardiovascular Drugs and Therapy Google Scholar. Article 

A multilocus genetic risk score for coronary heart disease: case-control and prospective cohort analyses.

Your email address is used only to let the recipient know who sent the email. Your feedback will go directly to Science X editors. PHG Foundation Aug 2019 Predictive accuracy of a polygenic risk score-enhanced prediction model vs a clinical risk score for coronary artery disease. Incremental predictive value of 152 single nucleotide polymorphisms in the 10-year risk prediction of incident coronary heart disease: the Rotterdam Study. Aragam KG, Dobbyn A, Judy R, Chaffin M, Chaudhary K, Hindy G, Cagan A, Finneran P, Weng LC, Loos RJF, Nadkarni G, Cho JH, Kember RL, Baras A, Reid J, Overton J, Philippakis A, Ellinor PT, Weiss ST, Rader DJ, Lubitz SA, Smoller JW, Karlson EW, Khera AV, Kathiresan S, Do R, Damrauer SM, Natarajan P. J Am Coll Cardiol. Association for Acute CardioVascular Care, European Association of Preventive Cardiology, European Association of Cardiovascular Imaging, European Association of Percutaneous Cardiovascular Interventions, Association of Cardiovascular Nursing & Allied Professions, Working Group on Atherosclerosis and Vascular Biology, Working Group on Cardiac Cellular Electrophysiology, Working Group on Pulmonary Circulation & Right Ventricular Function, Working Group on Aorta and Peripheral Vascular Diseases, Working Group on Myocardial & Pericardial Diseases, Working Group on Adult Congenital Heart Disease, Working Group on Development, Anatomy & Pathology, Working Group on Coronary Pathophysiology & Microcirculation, Working Group on Cellular Biology of the Heart, Working Group on Cardiovascular Pharmacotherapy, Working Group on Cardiovascular Regenerative and Reparative Medicine.

UL1 TR001881/TR/NCATS NIH HHS/United States, R01 HL142856/HL/NHLBI NIH HHS/United States, R01 HL132320/HL/NHLBI NIH HHS/United States, 16FTF30130005/AHA/American Heart Association-American Stroke Association/United States, U01 HG004402/HG/NHGRI NIH HHS/United States, P30 DK063491/DK/NIDDK NIH HHS/United States.

Nonetheless, it should not be assumed that adding polygenic risk scores in these populations will improve risk prediction. Subscription will auto renew annually. Lancet.

The researchers found that the polygenic risk score was associated with 10-year coronary heart disease incidence in both studies (hazard ratio per …

Department: University of Hong Kong.

Predictive Accuracy of a Polygenic Risk Score-Enhanced Prediction Model vs a Clinical Risk Score for Coronary Artery Disease. Brautbar A, Pompeii LA, Dehghan A, Ngwa JS, Nambi V, Virani SS, Rivadeneira F, Uitterlinden AG, Hofman A, Witteman JC, Pencina MJ, Folsom AR, Cupples LA, Ballantyne CM, Boerwinkle E. Atherosclerosis.

Natarajan P, Young R, Stitziel NO, Padmanabhan S, Baber U, Mehran R, et al. JAMA. Background. Here, we provide a short overview of the current research related to the possible application of PRS in clinical routine and critically discuss existing pitfalls, which still limit a widespread utility of PRS outside a research setting. N Engl J Med. 2020 Feb 18;323(7):614-615. doi: 10.1001/jama.2019.21667. Improvement in risk prediction of atherosclerotic cardiovascular disease (ASCVD) using information on the genetic predisposition at an individual level might offer new possibilities for the successful management of such complex trait. N Engl J Med. 2019;140:A16565. A genetic risk score based on direct associations with coronary heart disease improves coronary heart disease risk prediction in the Atherosclerosis Risk in Communities (ARIC), but not in the Rotterdam and Framingham Offspring, Studies. Wünnemann F, Sin Lo K, Langford-Avelar A, et al. Correspondence to Clipboard, Search History, and several other advanced features are temporarily unavailable.

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