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Circulating proteins and risk of small vessel stroke: A two-sample Mendelian randomization study
Ziwei Gao1,2, Yawen Xu1,2, Yue Chen1,2
1Department of Neurosurgery, Neurosurgery Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, China.
Medicine
|May 23, 2026
Summary
This study identified GRAMD1C as a circulating protein causally linked to increased small vessel stroke (SVS) risk. This finding suggests GRAMD1C as a potential biomarker for SVS diagnosis and therapy.
Area of Science:
- Genetics
- Neurology
- Biomarker Discovery
Background:
- Small vessel stroke (SVS) poses a significant health burden.
- Identifying reliable circulating biomarkers for SVS remains a challenge.
- Mendelian randomization (MR) offers a robust approach to investigate causal relationships.
Purpose of the Study:
- To systematically screen circulating proteins for potential causal associations with SVS risk.
- To identify novel protein biomarkers for SVS diagnosis and therapeutic targeting.
Main Methods:
- A two-sample Mendelian randomization (MR) design was employed.
- Utilized summary statistics from the MEGASTROKE Consortium (446,696 participants) and data on 4782 circulating proteins.
- Applied inverse variance weighting and sensitivity analyses for robust association estimates.
Main Results:
- GRAMD1C was identified as a circulating protein causally increasing SVS risk (OR=2.86, P=5.61e-05).
- PTGR1 showed a suggestive association with SVS risk (OR=1.15, P=6.65e-03).
- The cholesterol transporter GRAMD1C emerged as a significant risk factor for SVS.
Conclusions:
- GRAMD1C is a promising circulating biomarker for small vessel stroke.
- Targeting GRAMD1C may offer new avenues for SVS diagnosis and treatment.
- This MR study highlights the utility of proteomic data in understanding stroke etiology.
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