Plasma asparagine links to lower cardioembolic stroke risk
In Mendelian randomization, plasma free asparagine showed an odds ratio of 0.852 for cardioembolic stroke, whereas the glutamine-to-asparagine ratio yielded an odds ratio of 1.148.
IUBMB Life
In a European-ancestry study population, researchers used a two-sample Mendelian randomization framework to investigate causal links between 1,400 plasma metabolites and stroke risk. The team analyzed metabolite genome-wide association data from 3,441 to 8,299 individuals in the Canadian Longitudinal Study on Aging alongside stroke data from the MEGASTROKE consortium. Initial screening identified 235 nominal associations across 124 metabolites and ratios. After false-discovery-rate correction, plasma free asparagine was associated with lower cardioembolic stroke risk (odds ratio 0.852, 95% confidence interval 0.782 to 0.929). Conversely, the glutamine-to-asparagine ratio was associated with higher risk (odds ratio 1.148, 95% confidence interval 1.068 to 1.235). Additional nominal associations for steroid sulfates, bile-acid conjugates, and octadecenedioylcarnitine were supported by sensitivity analyses but did not survive multiple-testing correction.
Why it matters
Stroke is a primary contributor to global morbidity and mortality, yet its metabolic drivers remain poorly understood. Identifying causal roles for circulating amino-acid and lipid metabolites highlights potential targets for interventions against cerebrovascular disease.
Caveats
All findings were derived from datasets restricted to individuals of European ancestry. Furthermore, several metabolite associations were exploratory and failed to pass false-discovery-rate correction, requiring validation in larger and more diverse cohorts.
The paper
Causal Associations Between Plasma Metabolites and Stroke Risk Identified by Mendelian Randomization
Zhejiang Chinese Medical University · Guangzhou University of Chinese Medicine
IUBMB Life · 1 Oct 2026