The PCSK6-CORIN Polygenic Risk Score and Ischemic Stroke: The Dose-Response Association and Partial Mediation by Hypertension
Year: 2026
Type: article
Study design: Observational Study
Abstract: AIM: This study aimed to assess the association of single nucleotide polymorphisms (SNPs) in the PCSK6‑CORIN pathway with IS, the predictive ability of weighted genetic risk score (wGRS), and the mediating role of hypertension. METHODS: A total of 2,207 patients with IS and 2,590 community controls were included in this case-control study. The wGRS was developed using data from six TagSNPs in PCSK6 and CORIN. The associations, dose-response relationships, and mediation effects were assessed using logistic regression, restricted cubic spline, and mediation analyses. RESULTS: ). The plasma CORIN levels were significantly lower in patients with IS than in the controls (973.60±589.37 pg/mL vs. 1197.85±848.46 pg/mL, P = 0.043) in 88 IS and 88 controls. A history of hypertension appeared to partially mediate the effect of wGRS on IS, with a mediation proportion of 9.4% (95% CI: 5.0%-15.7%). CONCLUSIONS: Genetic variants in the PCSK6‑CORIN pathway are associated with IS risk, and the genetic risk may be partially mediated by hypertension.
DOI: 10.5551/jat.66291
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: diamond
Awards: G2190090696, G6459706697, G8827392221
OpenAlex ID: W7204261893