Genetic Risk Factors in Ischemic Stroke

The genetic architecture underlying ischaemic stroke encompasses both inherited and acquired components that influence susceptibility, severity and recovery. Common variants identified through genome-wide association studies have highlighted loci involved in lipid metabolism, coagulation cascades and vascular integrity. Rare variants, often observed in monogenic stroke syndromes, account for a minority of cases but have illuminated fundamental pathways such as arteriopathy and endothelial dysfunction. Polygenic risk scores aggregate the small effects of multiple loci, enabling stratification of at-risk individuals before clinical onset and informing preventive strategies. Beyond sequence variation, epigenetic modifications modulate gene expression in response to environmental stressors, contributing to interindividual differences in inflammatory response and neurovascular repair. Functional consequences of genetic variation manifest through altered platelet activation, blood–brain barrier permeability and neuronal survival mechanisms, shaping both acute outcomes and long-term disability. Integrating genetic profiling with clinical and imaging data is paving the way towards personalised stroke care, from anticipatory management in high-risk populations to targeted therapeutic interventions. Global consortia continue to expand the catalogue of stroke-associated alleles across diverse ethnicities, underscoring the importance of inclusive research frameworks to ensure equitable improvements in prevention and treatment.

Research from Nature Portfolio

A clinic–genetic study in a Middle Eastern cohort has demonstrated that common proinflammatory cytokine variants in the interleukin-10 and interleukin-1β genes significantly modulate ischaemic stroke risk. Specific genotypes of both loci were associated with increased susceptibility independent of traditional vascular factors, emphasising a central role for cytokine-mediated inflammation in stroke pathogenesis within this population. Earlier work employing DNA methylation clocks has revealed that an individual’s biological age, estimated via epigenome-wide methylation profiles, is a robust predictor of three-month mortality following acute ischaemic stroke. This finding highlights the interplay between genetic variation, epigenetic signatures and functional outcomes, and suggests that biological ageing measures may serve as integrated risk-stratification tools beyond chronological age.

Genetic Risk Factors in Ischemic Stroke publication trend

The graph below shows the total number of articles in genetic risk factors in ischemic stroke across all publications each year (not limited to Nature Index journals).

Technical terms

Single-nucleotide polymorphism (SNP): A variation of a single base in the DNA sequence among individuals that may influence disease risk or trait expression.

Genome-wide association study (GWAS): An approach scanning the entire genome for statistical associations between genetic variants and phenotypic traits or diseases.

Epigenetics: The study of heritable changes in gene function that occur without alterations in the DNA sequence, often through chemical modifications such as methylation.

DNA methylation: The addition of methyl groups to cytosine bases in DNA, modulating gene expression and serving as a biomarker of biological ageing or disease states.

Polygenic risk score: A quantitative estimate of an individual’s genetic susceptibility to a trait or disease, calculated by summing the effects of multiple risk alleles.

References

1. Interleukins 10 and 1β gene polymorphisms in ischemic stroke risk in the Egyptian population. Scientific Reports (2025).
2. Biological Age is a predictor of mortality in Ischemic Stroke. Scientific Reports (2018).
3. The Study of the Association of Polymorphisms in LSP1, GPNMB, PDPN, TAGLN, TSPO, and TUBB6 Genes with the Risk and Outcome of Ischemic Stroke in the Russian Population. International Journal of Molecular Sciences (2023).
4. Genome-wide association meta-analysis of functional outcome after ischemic stroke. Neurology (2019).
5. Genetics of ischemic stroke functional outcome. Journal of Neurology (2024).