10.5061/DRYAD.55HR85M
Sun, Daokun
The University of Texas Health Science Center at Houston
Tiedt, Steffen
Ludwig Maximilian University of Munich
Yu, Bing
The University of Texas Health Science Center at Houston
Jian, Xueqiu
The University of Texas Health Science Center at Houston
Gottesman, Rebecca F.
Johns Hopkins University
Mosley, Tom H.
University of Mississippi
Boerwinkle, Eric
The University of Texas Health Science Center at Houston
Dichgans, Martin
Ludwig Maximilian University of Munich
Fornage, Myriam
The University of Texas Health Science Center at Houston
Data from: A prospective study of serum metabolites and risk of ischemic stroke
Dryad
dataset
2019
Association studies in genetics
Cohort studies
Cerebrovascular disease/Stroke
2019-03-15T20:24:49Z
2019-03-15T20:24:49Z
en
https://doi.org/10.1212/wnl.0000000000007279
28856 bytes
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CC0 1.0 Universal (CC0 1.0) Public Domain Dedication
Objective: To identify promising blood-based biomarkers and novel
etiological pathways of disease risk, we applied an untargeted serum
metabolomics profiling in a community-based prospective study of ischemic
stroke (IS). Methods: In 3,904 men and women from the Atherosclerosis Risk
In Communities (ARIC) study, Cox proportional hazard models were used to
estimate the association of incident IS with the standardized level of 245
fasting serum metabolites individually, adjusting for age, sex, race,
field center, batch, diabetes, hypertension, current smoking status, body
mass index, and estimated glomerular filtration rate. Validation of
results was carried out in an independent sample of 114 IS cases and 112
healthy controls. Results: Serum levels of two long-chain dicarboxylic
acids, tetradecanedioate and hexadecanedioate, were strongly correlated
(r=0.88) and were associated with incident IS after adjusting for
covariates (Hazard Ratio [95% Confidence Interval (CI)] = 1.11 [1.06-1.16]
and 1.12 [1.07-1.17], respectively; p<0.0001). Analyses by IS
subtypes suggested that these associations were specific to cardioembolic
stroke (CES). Associations of tetradecanedioate and hexadecanedioate with
IS were independently confirmed (Odds Ratio [95% CI] = 1.76 [1.21; 2.56]
and 1.60 [1.11; 2.32], respectively). Conclusion: Two serum long-chain
dicarboxylic acids, metabolic products of ω-oxidation of fatty acids, were
associated with IS and CES independently of known risk factors. Pathways
related to intracellular hexadecanedioate synthesis or those involved in
its clearance from the circulation may mediate IS risk. These results
highlight the potential of metabolomics to discover novel circulating
biomarkers for stroke and to unravel novel pathways for IS and its
subtypes.
Supplemental InformationSupplemental files associated with
manuscriptSupplement 10-22-2018.docx