Lauren M Severance1, Hannah Carter2, Francisco J Contijoch3, Elliot R McVeigh4. 1. Department of Bioengineering, University of California-San Diego, San Diego, California, USA. 2. Department of Medicine, Medical Genetics Division, University of California-San Diego, San Diego, California, USA. 3. Department of Bioengineering, University of California-San Diego, San Diego, California, USA; Department of Radiology, University of California-San Diego, San Diego, California, USA. 4. Department of Bioengineering, University of California-San Diego, San Diego, California, USA; Department of Radiology, University of California-San Diego, San Diego, California, USA; Department of Medicine, Cardiovascular Division, University of California-San Diego, San Diego, California, USA. Electronic address: emcveigh@ucsd.edu.
Abstract
OBJECTIVES: The goal of this study was to assess the utility of a genetic risk score (GRS) in targeted coronary artery calcium (CAC) screening among young individuals. BACKGROUND: Early CAC screening and preventive therapy may reduce long-term risk of a coronary heart disease (CHD) event. However, identifying younger individuals at increased risk remains a challenge. GRS for CHD are age independent and can stratify individuals on various risk trajectories. METHODS: Using 142 variants associated with CHD events, we calculated a GRS in 1,927 individuals in the CARDIA (Coronary Artery Risk Development in Young Adults) cohort (aged 32 to 47 years) and 6,600 individuals in the MESA (Multi-Ethnic Study of Atherosclerosis) cohort (aged 44 to 87 years). We assessed GRS utility to predict CAC presence in the CARDIA cohort and stratify individuals of varying risk for CAC presence over the lifetime in both cohorts. RESULTS: The GRS predicted CAC presence in CARDIA males. It was not predictive in CARDIA females, which had a CAC prevalence of 6.4%. In combined analysis of the CARDIA and MESA cohorts, the GRS was predictive of CAC in both males and females and was used to derive an equation for the age at which CAC probability crossed a predetermined threshold. When assessed in combination with traditional risk factors, the GRS further stratified individuals. For individuals with an equal number of traditional risk factors, probability of CAC reached 25% approximately 10 years earlier for those in the highest GRS quintile compared to the lowest. CONCLUSIONS: The GRS may be used to target high-risk younger individuals for early CAC screening.
OBJECTIVES: The goal of this study was to assess the utility of a genetic risk score (GRS) in targeted coronary artery calcium (CAC) screening among young individuals. BACKGROUND: Early CAC screening and preventive therapy may reduce long-term risk of a coronary heart disease (CHD) event. However, identifying younger individuals at increased risk remains a challenge. GRS for CHD are age independent and can stratify individuals on various risk trajectories. METHODS: Using 142 variants associated with CHD events, we calculated a GRS in 1,927 individuals in the CARDIA (Coronary Artery Risk Development in Young Adults) cohort (aged 32 to 47 years) and 6,600 individuals in the MESA (Multi-Ethnic Study of Atherosclerosis) cohort (aged 44 to 87 years). We assessed GRS utility to predict CAC presence in the CARDIA cohort and stratify individuals of varying risk for CAC presence over the lifetime in both cohorts. RESULTS: The GRS predicted CAC presence in CARDIA males. It was not predictive in CARDIA females, which had a CAC prevalence of 6.4%. In combined analysis of the CARDIA and MESA cohorts, the GRS was predictive of CAC in both males and females and was used to derive an equation for the age at which CAC probability crossed a predetermined threshold. When assessed in combination with traditional risk factors, the GRS further stratified individuals. For individuals with an equal number of traditional risk factors, probability of CAC reached 25% approximately 10 years earlier for those in the highest GRS quintile compared to the lowest. CONCLUSIONS: The GRS may be used to target high-risk younger individuals for early CAC screening.
Authors: Gowtham R Grandhi; Mohammadhassan Mirbolouk; Zeina A Dardari; Mouaz H Al-Mallah; John A Rumberger; Leslee J Shaw; Ron Blankstein; Michael D Miedema; Daniel S Berman; Matthew J Budoff; Harlan M Krumholz; Michael J Blaha; Khurram Nasir Journal: JACC Cardiovasc Imaging Date: 2019-11-13
Authors: Sayantan Das; Lukas Forer; Sebastian Schönherr; Carlo Sidore; Adam E Locke; Alan Kwong; Scott I Vrieze; Emily Y Chew; Shawn Levy; Matt McGue; David Schlessinger; Dwight Stambolian; Po-Ru Loh; William G Iacono; Anand Swaroop; Laura J Scott; Francesco Cucca; Florian Kronenberg; Michael Boehnke; Gonçalo R Abecasis; Christian Fuchsberger Journal: Nat Genet Date: 2016-08-29 Impact factor: 38.330
Authors: Ruth McPherson; Alexander Pertsemlidis; Nihan Kavaslar; Alexandre Stewart; Robert Roberts; David R Cox; David A Hinds; Len A Pennacchio; Anne Tybjaerg-Hansen; Aaron R Folsom; Eric Boerwinkle; Helen H Hobbs; Jonathan C Cohen Journal: Science Date: 2007-05-03 Impact factor: 47.728
Authors: G S Berenson; W A Wattigney; R E Tracy; W P Newman; S R Srinivasan; L S Webber; E R Dalferes; J P Strong Journal: Am J Cardiol Date: 1992-10-01 Impact factor: 2.778
Authors: Diane E Bild; David A Bluemke; Gregory L Burke; Robert Detrano; Ana V Diez Roux; Aaron R Folsom; Philip Greenland; David R Jacob; Richard Kronmal; Kiang Liu; Jennifer Clark Nelson; Daniel O'Leary; Mohammed F Saad; Steven Shea; Moyses Szklo; Russell P Tracy Journal: Am J Epidemiol Date: 2002-11-01 Impact factor: 4.897
Authors: Matthew J Budoff; Rebekah Young; Gregory Burke; J Jeffrey Carr; Robert C Detrano; Aaron R Folsom; Richard Kronmal; Joao A C Lima; Kiang J Liu; Robyn L McClelland; Erin Michos; Wendy S Post; Steven Shea; Karol E Watson; Nathan D Wong Journal: Eur Heart J Date: 2018-07-01 Impact factor: 35.855
Authors: Christopher C Chang; Carson C Chow; Laurent Cam Tellier; Shashaank Vattikuti; Shaun M Purcell; James J Lee Journal: Gigascience Date: 2015-02-25 Impact factor: 6.524
Authors: Nilesh J Samani; Jeanette Erdmann; Alistair S Hall; Christian Hengstenberg; Massimo Mangino; Bjoern Mayer; Richard J Dixon; Thomas Meitinger; Peter Braund; H-Erich Wichmann; Jennifer H Barrett; Inke R König; Suzanne E Stevens; Silke Szymczak; David-Alexandre Tregouet; Mark M Iles; Friedrich Pahlke; Helen Pollard; Wolfgang Lieb; Francois Cambien; Marcus Fischer; Willem Ouwehand; Stefan Blankenberg; Anthony J Balmforth; Andrea Baessler; Stephen G Ball; Tim M Strom; Ingrid Braenne; Christian Gieger; Panos Deloukas; Martin D Tobin; Andreas Ziegler; John R Thompson; Heribert Schunkert Journal: N Engl J Med Date: 2007-07-18 Impact factor: 91.245
Authors: Quinn S Wells; Minoo Bagheri; Aaron W Aday; Deepak K Gupta; Christian M Shaffer; Wei-Qi Wei; Nataraja Sarna Vaitinadin; Sadiya S Khan; Philip Greenland; Thomas J Wang; C Michael Stein; Dan M Roden; Jonathan D Mosley Journal: Circ Genom Precis Med Date: 2021-08-31
Authors: Omar Dzaye; Alexander C Razavi; Zeina A Dardari; Leslee J Shaw; Daniel S Berman; Matthew J Budoff; Michael D Miedema; Khurram Nasir; Alan Rozanski; John A Rumberger; Carl E Orringer; Sidney C Smith; Ron Blankstein; Seamus P Whelton; Martin Bødtker Mortensen; Michael J Blaha Journal: J Am Coll Cardiol Date: 2021-10-19 Impact factor: 27.203
Authors: Aamir Javaid; Zeina A Dardari; Joshua D Mitchell; Seamus P Whelton; Omar Dzaye; Joao A C Lima; Donald M Lloyd-Jones; Matthew Budoff; Khurram Nasir; Daniel S Berman; John Rumberger; Michael D Miedema; Todd C Villines; Michael J Blaha Journal: J Am Coll Cardiol Date: 2022-05-17 Impact factor: 27.203
Authors: Evan D Muse; Shang-Fu Chen; Shuchen Liu; Brianna Fernandez; Brian Schrader; Bhuvan Molparia; André Nicolás León; Raymond Lee; Neha Pubbi; Nolan Mejia; Christina Ren; Ahmed El-Kalliny; Ernesto Prado Montes de Oca; Hector Aguilar; Arjun Ghoshal; Raquel Dias; Doug Evans; Kai-Yu Chen; Yunyue Zhang; Nathan E Wineinger; Emily G Spencer; Eric J Topol; Ali Torkamani Journal: NPJ Digit Med Date: 2022-03-11