Observational studyNeurology2022
Nucleosides Associated With Incident Ischemic Stroke in the REGARDS and JHS Cohorts.
Open access · greenAbstract readObservational Study
In one paragraph
Observational study in Neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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0cells of the map it votes in
20citing papers in PubMed
3.4field-weighted citation impact, top 7% of its field
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 21 citations in OpenAlex.
- Workplace food purchases, dietary intake, and gut microbial metabolites in a secondary analysis of the ChooseWell 365 study.The American journal of clinical nutrition · 2024Trial
- Plasma Metabolites Link Dietary Patterns to Stroke Risk.Annals of neurology · 2023Trial
- A Reporting Guideline for Observational Studies in Metabolomic Epidemiology: Explanation and Elaboration of the Strobe-MetEpi Checklist.Research square · 2026Article
- Fibrinogen-associated plasma metabolites and implications for coagulation, inflammation, and vascular diseases.Journal of thrombosis and haemostasis : JTH · 2026Article
- A metabolite index of ultra-processed food intake is associated with stroke, cancer mortality, and all-cause mortality.medRxiv : the preprint server for health sciences · 2026Article
- Omega-3 Fatty Acids and Risk of Ischemic Stroke in REGARDS.Translational stroke research · 2025Article
- Association of gut microbiota and immunometabolic profiles with ischemic stroke severity.Scientific reports · 2025Article
- Targeted Metabolomics in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study.Scientific data · 2025Article
- Acetylglutamine Differentially Associated with First-Time Versus Recurrent Stroke.Translational stroke research · 2024Observational
- The Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) Diet and Metabolites in Chronic Kidney Disease.Nutrients · 2024Article
- Associations of Plasma Metabolites With Risks of Incident Stroke and Its Subtypes in Chinese Adults.Journal of the American Heart Association · 2024Article
- Sex-Associated Metabolites and Incident Stroke, Incident Coronary Heart Disease, Hypertension, and Chronic Kidney Disease in the REGARDS Cohort.Journal of the American Heart Association · 2024Article
- Plasma Metabolites and Life's Simple 7 in REGARDS.Stroke · 2024Article
- Unraveling Metabolic Changes following Stroke: Insights from a Urinary Metabolomics Analysis.Metabolites · 2024Article
- Causal relationship between human blood metabolites and risk of ischemic stroke: a Mendelian randomization study.Frontiers in genetics · 2024Article
- Metabolomic epidemiology offers insights into disease aetiology.Nature metabolism · 2023Review
- Trimethylamine N-Oxide and White Matter Hyperintensity Volume Among Patients With Acute Ischemic Stroke.JAMA network open · 2023Observational
- Gut microbiota-associated metabolites and risk of ischemic stroke in REGARDS.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Article
- Association of Circulating Metabolites With Racial Disparities in Hypertension and Stroke in the REGARDS Study.Neurology · 2023Article
- Metabolite profiles and DNA methylation in metabolic syndrome: a two-sample, bidirectional Mendelian randomization.Frontiers in genetics · 2023Article
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Zsuzsanna AmentFrom the Center for Genomic Medicine, Harvard Medical School (Z.A., W.T.K.), and Department of Neurology (Z.A., A.-L.G.G., W.T.K.), Massachusetts General Hospital, Boston; Departments of Epidemiology (A.P., N.C., R.M.I.) and Biostatistics (S.E.J., L.L.), School of Public Health, University of Alabama at Birmingham; Harvard Medical School (V.M.B.), Boston, MA; The Jackson Heart Study (Y.G., A.C.), University of Mississippi Medical Center, Jackson; Department of Medicine (R.E.G.), Beth Israel Deaconess Medical Center, Boston, MA; and Department of Medicine (M.C.), Larner College of Medicine at the University of Vermont, Burlington.ORCID 0000-0002-0316-4348
Amit PatkiFrom the Center for Genomic Medicine, Harvard Medical School (Z.A., W.T.K.), and Department of Neurology (Z.A., A.-L.G.G., W.T.K.), Massachusetts General Hospital, Boston; Departments of Epidemiology (A.P., N.C., R.M.I.) and Biostatistics (S.E.J., L.L.), School of Public Health, University of Alabama at Birmingham; Harvard Medical School (V.M.B.), Boston, MA; The Jackson Heart Study (Y.G., A.C.), University of Mississippi Medical Center, Jackson; Department of Medicine (R.E.G.), Beth Israel Deaconess Medical Center, Boston, MA; and Department of Medicine (M.C.), Larner College of Medicine at the University of Vermont, Burlington.
Ninad ChaudharyFrom the Center for Genomic Medicine, Harvard Medical School (Z.A., W.T.K.), and Department of Neurology (Z.A., A.-L.G.G., W.T.K.), Massachusetts General Hospital, Boston; Departments of Epidemiology (A.P., N.C., R.M.I.) and Biostatistics (S.E.J., L.L.), School of Public Health, University of Alabama at Birmingham; Harvard Medical School (V.M.B.), Boston, MA; The Jackson Heart Study (Y.G., A.C.), University of Mississippi Medical Center, Jackson; Department of Medicine (R.E.G.), Beth Israel Deaconess Medical Center, Boston, MA; and Department of Medicine (M.C.), Larner College of Medicine at the University of Vermont, Burlington.ORCID 0000-0003-1350-1093
Varun M BhaveFrom the Center for Genomic Medicine, Harvard Medical School (Z.A., W.T.K.), and Department of Neurology (Z.A., A.-L.G.G., W.T.K.), Massachusetts General Hospital, Boston; Departments of Epidemiology (A.P., N.C., R.M.I.) and Biostatistics (S.E.J., L.L.), School of Public Health, University of Alabama at Birmingham; Harvard Medical School (V.M.B.), Boston, MA; The Jackson Heart Study (Y.G., A.C.), University of Mississippi Medical Center, Jackson; Department of Medicine (R.E.G.), Beth Israel Deaconess Medical Center, Boston, MA; and Department of Medicine (M.C.), Larner College of Medicine at the University of Vermont, Burlington.
Ana-Lucia Garcia GuarnizFrom the Center for Genomic Medicine, Harvard Medical School (Z.A., W.T.K.), and Department of Neurology (Z.A., A.-L.G.G., W.T.K.), Massachusetts General Hospital, Boston; Departments of Epidemiology (A.P., N.C., R.M.I.) and Biostatistics (S.E.J., L.L.), School of Public Health, University of Alabama at Birmingham; Harvard Medical School (V.M.B.), Boston, MA; The Jackson Heart Study (Y.G., A.C.), University of Mississippi Medical Center, Jackson; Department of Medicine (R.E.G.), Beth Israel Deaconess Medical Center, Boston, MA; and Department of Medicine (M.C.), Larner College of Medicine at the University of Vermont, Burlington.
Yan GaoFrom the Center for Genomic Medicine, Harvard Medical School (Z.A., W.T.K.), and Department of Neurology (Z.A., A.-L.G.G., W.T.K.), Massachusetts General Hospital, Boston; Departments of Epidemiology (A.P., N.C., R.M.I.) and Biostatistics (S.E.J., L.L.), School of Public Health, University of Alabama at Birmingham; Harvard Medical School (V.M.B.), Boston, MA; The Jackson Heart Study (Y.G., A.C.), University of Mississippi Medical Center, Jackson; Department of Medicine (R.E.G.), Beth Israel Deaconess Medical Center, Boston, MA; and Department of Medicine (M.C.), Larner College of Medicine at the University of Vermont, Burlington.
Robert E GersztenFrom the Center for Genomic Medicine, Harvard Medical School (Z.A., W.T.K.), and Department of Neurology (Z.A., A.-L.G.G., W.T.K.), Massachusetts General Hospital, Boston; Departments of Epidemiology (A.P., N.C., R.M.I.) and Biostatistics (S.E.J., L.L.), School of Public Health, University of Alabama at Birmingham; Harvard Medical School (V.M.B.), Boston, MA; The Jackson Heart Study (Y.G., A.C.), University of Mississippi Medical Center, Jackson; Department of Medicine (R.E.G.), Beth Israel Deaconess Medical Center, Boston, MA; and Department of Medicine (M.C.), Larner College of Medicine at the University of Vermont, Burlington.
Adolfo CorreaFrom the Center for Genomic Medicine, Harvard Medical School (Z.A., W.T.K.), and Department of Neurology (Z.A., A.-L.G.G., W.T.K.), Massachusetts General Hospital, Boston; Departments of Epidemiology (A.P., N.C., R.M.I.) and Biostatistics (S.E.J., L.L.), School of Public Health, University of Alabama at Birmingham; Harvard Medical School (V.M.B.), Boston, MA; The Jackson Heart Study (Y.G., A.C.), University of Mississippi Medical Center, Jackson; Department of Medicine (R.E.G.), Beth Israel Deaconess Medical Center, Boston, MA; and Department of Medicine (M.C.), Larner College of Medicine at the University of Vermont, Burlington.ORCID 0000-0002-9501-600X
Suzanne E JuddFrom the Center for Genomic Medicine, Harvard Medical School (Z.A., W.T.K.), and Department of Neurology (Z.A., A.-L.G.G., W.T.K.), Massachusetts General Hospital, Boston; Departments of Epidemiology (A.P., N.C., R.M.I.) and Biostatistics (S.E.J., L.L.), School of Public Health, University of Alabama at Birmingham; Harvard Medical School (V.M.B.), Boston, MA; The Jackson Heart Study (Y.G., A.C.), University of Mississippi Medical Center, Jackson; Department of Medicine (R.E.G.), Beth Israel Deaconess Medical Center, Boston, MA; and Department of Medicine (M.C.), Larner College of Medicine at the University of Vermont, Burlington.ORCID 0000-0001-7594-6587
Mary CushmanFrom the Center for Genomic Medicine, Harvard Medical School (Z.A., W.T.K.), and Department of Neurology (Z.A., A.-L.G.G., W.T.K.), Massachusetts General Hospital, Boston; Departments of Epidemiology (A.P., N.C., R.M.I.) and Biostatistics (S.E.J., L.L.), School of Public Health, University of Alabama at Birmingham; Harvard Medical School (V.M.B.), Boston, MA; The Jackson Heart Study (Y.G., A.C.), University of Mississippi Medical Center, Jackson; Department of Medicine (R.E.G.), Beth Israel Deaconess Medical Center, Boston, MA; and Department of Medicine (M.C.), Larner College of Medicine at the University of Vermont, Burlington.ORCID 0000-0002-7871-6143
D Leann LongFrom the Center for Genomic Medicine, Harvard Medical School (Z.A., W.T.K.), and Department of Neurology (Z.A., A.-L.G.G., W.T.K.), Massachusetts General Hospital, Boston; Departments of Epidemiology (A.P., N.C., R.M.I.) and Biostatistics (S.E.J., L.L.), School of Public Health, University of Alabama at Birmingham; Harvard Medical School (V.M.B.), Boston, MA; The Jackson Heart Study (Y.G., A.C.), University of Mississippi Medical Center, Jackson; Department of Medicine (R.E.G.), Beth Israel Deaconess Medical Center, Boston, MA; and Department of Medicine (M.C.), Larner College of Medicine at the University of Vermont, Burlington.ORCID 0000-0001-8614-7190
M Ryan IrvinFrom the Center for Genomic Medicine, Harvard Medical School (Z.A., W.T.K.), and Department of Neurology (Z.A., A.-L.G.G., W.T.K.), Massachusetts General Hospital, Boston; Departments of Epidemiology (A.P., N.C., R.M.I.) and Biostatistics (S.E.J., L.L.), School of Public Health, University of Alabama at Birmingham; Harvard Medical School (V.M.B.), Boston, MA; The Jackson Heart Study (Y.G., A.C.), University of Mississippi Medical Center, Jackson; Department of Medicine (R.E.G.), Beth Israel Deaconess Medical Center, Boston, MA; and Department of Medicine (M.C.), Larner College of Medicine at the University of Vermont, Burlington.
W Taylor KimberlyFrom the Center for Genomic Medicine, Harvard Medical School (Z.A., W.T.K.), and Department of Neurology (Z.A., A.-L.G.G., W.T.K.), Massachusetts General Hospital, Boston; Departments of Epidemiology (A.P., N.C., R.M.I.) and Biostatistics (S.E.J., L.L.), School of Public Health, University of Alabama at Birmingham; Harvard Medical School (V.M.B.), Boston, MA; The Jackson Heart Study (Y.G., A.C.), University of Mississippi Medical Center, Jackson; Department of Medicine (R.E.G.), Beth Israel Deaconess Medical Center, Boston, MA; and Department of Medicine (M.C.), Larner College of Medicine at the University of Vermont, Burlington.ORCID 0000-0002-2519-8530
Harvard University · US
Funding
VCID and Stroke in a Bi-racial National CohortU01NS041588 · NINDS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI CUSHMAN, MARY, HOWARD, GEORGE · 2002 to 2022
$96.0MVermont Center for Cardiovascular and Brain HealthP20GM135007 · NIGMS · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI Kathryn H Morelli · 2020 to 2026
$17.4MMetabolomic predictors of stroke in REGARDSR01NS099209 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI KIMBERLY, WILLIAM TAYLOR · 2017 to 2021
$2.4MNHLBI NIH HHS HHSN268201800010INHLBI NIH HHS HHSN268201800011INHLBI NIH HHS HHSN268201800012INHLBI NIH HHS HHSN268201800014INHLBI NIH HHS HHSN268201800015INIGMS NIH HHS P20 GM135007NIMHD NIH HHS HHSN268201800013ININDS NIH HHS R01 NS099209NINDS NIH HHS U01 NS041588
Abstract
BACKGROUND AND
objectivesBoth genetic and environmental factors contribute to stroke risk. We sought to identify novel metabolites associated with incident stroke in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort and determine whether they reflected genetic or environmental variation.
methodsThis was a stroke case-cohort observational study nested in REGARDS. Cases were defined as incident stroke and metabolomic profiles were compared to a randomly selected control cohort. In baseline plasma samples, 162 metabolites were measured using liquid chromatography-tandem mass spectrometry. Cox proportional hazards models were adjusted for age, sex, race, and age by race in the base model. Fully adjusted models included traditional stroke risk factors. Mediation analyses conducted for these stroke risk factors used the metabolite as mediator. Genome-wide associations with the leading candidate metabolites were calculated using array data. Replication analyses in the Jackson Heart Study (JHS) were conducted using random effects meta-analysis.
resultsThere were 2,043 participants who were followed over an average period of 7.1 years, including 1,075 stroke cases and 968 random controls. Nine metabolites were associated with stroke in the base model, 8 of which were measured and remained significant in meta-analysis with JHS. In the fully adjusted model in REGARDS, guanosine (hazard ratio [HR] 1.34, 95% CI 1.18-1.53; DISCUSSION: Guanosine and pseudouridine are nucleosides associated with incident ischemic stroke independently of other risk factors. Genetic and mediation analyses suggest that environmental exposures rather than genetic variation link nucleoside levels to stroke risk. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that guanosine and pseudouridine are associated with incident stroke.
Indexed as
Coronary DiseaseIschemic StrokeStrokeCase-Control StudiesGenome-Wide Association StudyGuanosineHumansIncidenceLongitudinal StudiesNucleosidesPseudouridineRisk FactorsGuanosineNucleosidesPseudouridine
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