Multi-omic analysis of stroke recurrence in African Americans from the Vitamin Intervention for Stroke Prevention (VISP) clinical trial
Open Access
- 4 March 2021
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 16 (3), e0247257
- https://doi.org/10.1371/journal.pone.0247257
Abstract
African Americans endure a nearly two-fold greater risk of suffering a stroke and are 2–3 times more likely to die from stroke compared to those of European ancestry. African Americans also have a greater risk of recurrent stroke and vascular events, which are deadlier and more disabling than incident stroke. Stroke is a multifactorial disease with both heritable and environmental risk factors. We conducted an integrative, multi-omic study on 922 plasma metabolites, 473,864 DNA methylation loci, and 556 variants from 50 African American participants of the Vitamin Intervention for Stroke Prevention clinical trial to help elucidate biomarkers contributing to recurrent stroke rates in this high risk population. Sixteen metabolites, including cotinine, N-delta-acetylornithine, and sphingomyelin (d17:1/24:1) were identified in t-tests of recurrent stroke outcome or baseline smoking status. Serum tricosanoyl sphingomyelin (d18:1/23:0) levels were significantly associated with recurrent stroke after adjusting for covariates in Cox Proportional Hazards models. Weighted Gene Co-expression Network Analysis identified moderate correlations between sphingolipid markers and clinical traits including days to recurrent stroke. Integrative analyses between genetic variants in sphingolipid pathway genes identified 29 nominal associations with metabolite levels in a one-way analysis of variance, while epigenomic analyses identified xenobiotics, predominately smoking-associated metabolites and pharmaceutical drugs, associated with methylation profiles. Taken together, our results suggest that metabolites, specifically those associated with sphingolipid metabolism, are potential plasma biomarkers for stroke recurrence in African Americans. Furthermore, genetic variation and DNA methylation may play a role in the regulation of these metabolites.Funding Information
- National Human Genome Research Institute (U01HG005160)
- National Human Genome Research Institute (U01HG005160)
- National Human Genome Research Institute (U01HG005160-03S1)
- National Human Genome Research Institute (U01HG005160-03S1)
- National Institute of Neurological Disorders and Stroke (R15 NS095115-01A1)
- National Institute of Neurological Disorders and Stroke (R15 NS095115-01A1)
- National Institute of Neurological Disorders and Stroke (R15NS095115-01A1S1)
- National Institute of Neurological Disorders and Stroke (R15NS095115-01A1S1)
- American Heart Association (Scientist Development Award 12SDG9180012)
- Walking for My Life 5K Stroke Walk sponsored by Faith Christian Center International
- National Institute of Neurological Disorders and Stroke (R01NS34447)
This publication has 36 references indexed in Scilit:
- Heart Disease and Stroke Statistics—2020 Update: A Report From the American Heart AssociationJournal of the American College of Cardiology, 2020
- A prospective study of serum metabolites and risk of ischemic strokeNeurology, 2019
- Stroke in Indigenous Africans, African Americans, and European AmericansStroke, 2017
- Discovery of Metabolite Biomarkers for Acute Ischemic Stroke ProgressionJournal of Proteome Research, 2017
- Aetiological blood biomarkers of ischaemic strokeSwiss Medical Weekly, 2015
- Genome-Wide Meta-Analysis of Homocysteine and Methionine Metabolism Identifies Five One Carbon Metabolism Loci and a Novel Association of ALDH1L1 with Ischemic StrokePLoS Genetics, 2014
- A metabonomic approach applied to predict patients with cerebral infarctionTalanta, 2011
- Integrated, Nontargeted Ultrahigh Performance Liquid Chromatography/Electrospray Ionization Tandem Mass Spectrometry Platform for the Identification and Relative Quantification of the Small-Molecule Complement of Biological SystemsAnalytical Chemistry, 2009
- Regional Differences in African Americans' High Risk for Stroke: The Remarkable Burden of Stroke for Southern African AmericansAnnals of Epidemiology, 2007
- Vitamin intervention for stroke preventionJournal of the Neurological Sciences, 2002