The PCSK6-CORIN Polygenic Risk Score and Ischemic Stroke: The Dose-Response Association and Partial Mediation by Hypertension
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.
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BibTeX
@article{fang2026pcsk6corin,
title = {{The PCSK6-CORIN Polygenic Risk Score and Ischemic Stroke: The Dose-Response Association and Partial Mediation by Hypertension}},
author = {Zhengmei Fang and Tao Zhang and Lijun Zhu and Yuelong Jin and Yan Chen and Yingshui Yao},
journal = {Journal of Atherosclerosis and Thrombosis},
year = {2026},
month = aug,
doi = {10.5551/jat.66291},
url = {https://www.jstage.jst.go.jp/article/jat/advpub/0/advpub_66291/_article},
note = {CC BY-NC-SA},
}
RIS
TY - JOUR
TI - The PCSK6-CORIN Polygenic Risk Score and Ischemic Stroke: The Dose-Response Association and Partial Mediation by Hypertension
AU - Zhengmei Fang
AU - Tao Zhang
AU - Lijun Zhu
AU - Yuelong Jin
AU - Yan Chen
AU - Yingshui Yao
PY - 2026
DA - 2026/08/27
JO - Journal of Atherosclerosis and Thrombosis
DO - 10.5551/jat.66291
UR - https://www.jstage.jst.go.jp/article/jat/advpub/0/advpub_66291/_article
AB - 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.
SN - 1880-3873
SN - 1340-3478
ER -