A genome-wide association study of stroke risk in Asian statin users: evidence from KoGES and UK Biobank.

IF 1.9 4区医学 Q3 PHARMACOLOGY & PHARMACY

Pharmacogenomics Pub Date : 2025-09-15 DOI:10.1080/14622416.2025.2558499

Da Hoon Lee, Yoon-A Park, Jung Sun Kim, Yubin Song, SeungJin Bae, Jeong Yee, Hye Sun Gwak

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引用次数: 0

Abstract

Background: Despite proven efficacy of statins in stroke prevention, genetic factors may influence individual stroke risk among statin users. With increasing precision medicine approaches and growing evidence of population-specific genetic variations, identifying genetic markers that predict stroke risk in statin-treated Asian populations has become critically important for personalized cardiovascular prevention strategies.

Methods: We conducted a genome-wide association study of 1,678 participants using lipid-lowering agents in the Korean Genome and Epidemiology Study (KoGES) cohort. Significant findings were replicated in 2,170 Asian participants on statins from the UK Biobank using an additive genetic model adjusted for relevant covariates.

Results: In the discovery analysis, 83 single nucleotide polymorphisms were suggestively associated with stroke (p <1.0 × 10^-5). Among these, 21 SNPs in the CDH13 gene were associated with increased stroke risk. The lead SNP, rs7201829, was significantly replicated in the UK Biobank (odds ratio: 2.29, p = 2.39 × 10^-5).

Conclusions: This study identified CDH13 as a significant genetic marker associated with stroke risk among Asian statin users. These findings provide the first genome-wide evidence for genetic determinants of stroke susceptibility during statin therapy, supporting the development of personalized prevention strategies in Asian populations.

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亚洲他汀类药物使用者中风风险的全基因组关联研究：来自KoGES和UK Biobank的证据。

背景：尽管他汀类药物在预防脑卒中方面已被证实有效，但遗传因素可能影响他汀类药物使用者的个体脑卒中风险。随着越来越多的精准医学方法和越来越多的人群特异性遗传变异的证据，识别预测他汀类药物治疗的亚洲人群中风风险的遗传标记对于个性化心血管预防策略至关重要。方法：我们在韩国基因组和流行病学研究（KoGES）队列中对1,678名使用降脂药物的参与者进行了全基因组关联研究。在英国生物银行2170名服用他汀类药物的亚洲参与者中，使用校正相关变量的加性遗传模型重复了重要的发现。结果：在发现分析中，83个单核苷酸多态性与脑卒中相关（p -5）。其中，CDH13基因中的21个snp与卒中风险增加有关。先导SNP rs7201829在UK Biobank中被显著复制（优势比：2.29,p = 2.39 × 10-5）。结论：本研究确定CDH13是与亚洲他汀类药物使用者中风风险相关的重要遗传标记。这些发现为他汀类药物治疗期间卒中易感性的遗传决定因素提供了第一个全基因组证据，支持亚洲人群个性化预防策略的发展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pharmacogenomics 医学-药学

CiteScore

3.40

自引率

9.50%

发文量

审稿时长

4-8 weeks

期刊介绍： Pharmacogenomics (ISSN 1462-2416) is a peer-reviewed journal presenting reviews and reports by the researchers and decision-makers closely involved in this rapidly developing area. Key objectives are to provide the community with an essential resource for keeping abreast of the latest developments in all areas of this exciting field. Pharmacogenomics is the leading source of commentary and analysis, bringing you the highest quality expert analyses from corporate and academic opinion leaders in the field.