Association of a Multiancestry Genome-Wide Blood Pressure Polygenic Risk Score With Adverse Cardiovascular Events
Year: 2022
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Traditional cardiovascular risk factors and the underlying genetic risk of elevated blood pressure (BP) determine an individual's composite risk of developing adverse cardiovascular events. We sought to evaluate the relative contributions of the traditional cardiovascular risk factors to the development of adverse cardiovascular events in the context of varying BP genetic risk profiles. METHODS: Genome-wide polygenic risk score (PRS) was computed using multiancestry genome-wide association estimates among US adults who underwent whole-genome sequencing in the Trans-Omics for Precision program. Individuals were stratified into high, intermediate, and low genetic risk groups (>80th, 20-80th, and <20th centiles of systolic BP [SBP] PRS). Based on the ACC/AHA Pooled Cohort Equations, participants were stratified into low and high (10 year-atherosclerotic cardiovascular disease [CVD] risk: <10% or ≥10%) cardiovascular risk factor profile groups. The primary study outcome was incident cardiovascular event (composite of incident heart failure, incident stroke, and incident coronary heart disease). RESULTS: Among 21 897 US adults (median age: 56 years; 56.0% women; 35.8% non-White race/ethnicity), 1 SD increase in the SBP PRS, computed using 1.08 million variants, was associated with SBP (β: 4.39 [95% CI, 4.13-4.65]) and hypertension (odds ratio, 1.50 [95% CI, 1.46-1.55]), respectively. This association was robustly seen across racial/ethnic groups. Each SD increase in SBP PRS was associated with a higher risk of the incident CVD (multivariable-adjusted hazards ratio, 1.07 [95% CI, 1.04-1.10]) after controlling for ACC/AHA Pooled Cohort Equations risk scores. Among individuals with a high SBP PRS, low atherosclerotic CVD risk was associated with a 58% lower hazard for incident CVD (multivariable-adjusted hazards ratio, 0.42 [95% CI, 0.36-0.50]) compared to those with high atherosclerotic CVD risk. A similar pattern was noted in intermediate and low genetic risk groups. CONCLUSIONS: In a multiancestry cohort of >21 000 US adults, genome-wide SBP PRS was associated with BP traits and adverse cardiovascular events. Adequate control of modifiable cardiovascular risk factors may reduce the predisposition to adverse cardiovascular events among those with a high SBP PRS.
Institutions: University of Alabama at Birmingham, UAB Medicine, Broad Institute, Harvard University, Massachusetts General Hospital, Massachusetts Institute of Technology, University of California, Los Angeles, The Lundquist Institute, Harbor–UCLA Medical Center, University of Virginia, Birmingham VA Medical Center
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
Funders: Doris Duke Charitable Foundation, Abbott Laboratories, AstraZeneca, GlaxoSmithKline, Sanofi, Omron Healthcare, Bayer HealthCare, Novo Nordisk, National Institutes of Health, National Institute on Aging, National Heart, Lung, and Blood Institute, National Human Genome Research Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Advancing Translational Sciences, National Institute on Minority Health and Health Disparities
Awards: G1114307781, G1220223050, G1261314546, MESA, CORONARY HEART DISEASE AND STROKE, CORONARY HEART DISEASE &STROKE IN PEOPLE AGED 65-84, G1409423729, G1539384734, G1609525565, CORONARY HEART DISEASE AND STROKE, G1679056238, G1686417863, G1803853571, Healthy Americas: All of Us Research Program, Large Scale Sequencing and Analysis of Genomes, Rare variants and NHLBI traits in deeply phenotyped cohorts, G2194386449, CORONARY HEART DISEASE &STROKE IN PEOPLE AGED 65-84, G2262782284, G2316258288, G232264632, G2391884931, G2415573643, MESA, G247538147, G2544667880, G2580996367, CORONARY HEART DISEASE &STROKE IN THE ELDERLY, G278200998, G2809357584, MESA, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY--EBCT READING, G297113894, G3045517347, G3220743633, G3256118428, G3342643523, G3405256882, G343705321, G350245564, CHS research resources for the cardiovascular health of older adults, G3570589137, G3647016462, G3687594596, MESA, G3973572274, CENTRAL BLOOD ANALYSIS LABORATORY FOR CHS, G399481048, Rare variants and NHLBI traits in deeply phenotyped cohorts, G4223531873, TITLE: MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS (MESA), G4429312988, G4512137732, G4563812999, G47192932, G4747441672, G4790942633, OPTION 3. 4/1/2014 - 3/31/2015. MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS (MESA) - READING CENTER, NHLBI, MESA, G4976486911, G50080621, G5088122703, G5108002584, G514410172, G5164707915, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY-ULTRASOUND, G522046365, G5479317095, University of Arizona-Banner Health All of Us Research Program , G5770678025, G5787256936, G579045871, G581887176, G5928944960, CHS Events Follow-up Study, G6095866717, G6226795708, G6359107525, Institute for Clinical and Translational Research, The Framingham Heart Study, MESA, G6514094751, CHS-Transition Phase, SNP HEALTH ASSOCIATION RESOURCE (SHARE), G6837735701, G7032370290, G7091571603, G7155745631, G7176672723, MESA, SouthEast Enrollment Center (SEEC) , G7535686976, Clinical and Translational Science Award, Studies of Rare Genetic Variation in the Isolated Population of Sardinia, G8738262636, G8761005068, G89699440, G9000004253, G9000006085, G9000011423, G9000013175, G9000021463, G9000021538, G9000035207, G9000041420, G9000051044, G9000055272, G9000063695, G9000063797, G9000076419, G9000077829, G9000085573, G9000128449, G9000290334, G9000303384, Diabetes Research Center (DRC), Natriuretic Peptide-Renin-Angiotensin-Aldosterone System Rhythm Axis and Nocturnal Blood Pressure, UCLA Clinical and Translational Science Institute, The Effects of Neprilysin Inhibition on Cardiometabolic Health in Black Individuals, G94668252
OpenAlex ID: W4308294089