# The Role of Genetics in Stroke Risk and Outcome: A Review of Current Evidence

## TL;DR

This paper reviews how genetics influence stroke risk and recovery, highlighting genes and pathways that could improve prevention and treatment strategies.

## Contribution

The paper synthesizes current evidence on genetic factors affecting stroke risk and outcomes, including GWAS, rare mutations, and epigenetic mechanisms.

## Key findings

- Genetic variants influence stroke susceptibility, severity, and treatment response beyond traditional risk factors.
- Common and rare genetic mutations in coagulation, inflammation, and lipid metabolism pathways contribute to stroke risk.
- Epigenetic modifications like DNA methylation and non-coding RNAs affect stroke vulnerability and recovery.

## Abstract

Stroke affects over 15 million people annually, with genetic factors significantly influencing risk and recovery. Understanding the complex interplay of factors contributing to stroke is crucial for developing effective prevention and treatment strategies.

This review aims to synthesize current evidence regarding the genetic underpinnings of both stroke risk and outcome, encompassing ischemic stroke, hemorrhagic stroke, and specific stroke subtypes. Genetic factors uniquely explain variability in stroke risk and treatment response beyond traditional factors like hypertension. We examine the roles of common genetic variants identified through genome‐wide association studies (GWAS), the influence of rare, high‐impact mutations implicated in monogenic stroke disorders, and the contribution of epigenetic modifications to stroke vulnerability and recovery. Furthermore, we explore the impact of genes involved in key pathways such as coagulation, inflammation, lipid metabolism, and cerebrovascular structure and function.

This review highlights the growing body of evidence associating specific genetic variants with increased stroke susceptibility, altered stroke severity, and differential responses to treatment. These findings have the potential to refine risk stratification strategies, identify novel therapeutic targets, and personalize stroke management based on individual genetic profiles.

Future research should focus on replicating findings across diverse populations, elucidating gene–environment interactions, and translating genetic discoveries into clinically actionable tools for stroke prevention and improved patient outcomes.

This study delineates the multiple pathways leading to stroke, encompassing genetic risk factors such as lipid/cholesterol metabolism, blood pressure regulation genes, and endothelial dysfunction. The report includes genetic pathways such as Val66Met polymorphism, prothrombin G20210A, interleukin‐6 and tumor necrosis factor gene variant, along with pharmacogenomics pathways that explain drug responses (e.g., aspirin and warfarin), resistance, and prognostic predictors that help assess stroke outcomes. We also included explanations for atherophysiology, oxidative stress, and cell death, as well as epigenetic mechanisms, such as DNA methylation, histone modification, and non‐coding RNAs.