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Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
Identification of Novel Genetic Risk Variants Associated With Early-Onset Ischemic Stroke in Taiwan
Yin-Cheng Wang1,2,3, Kai-Ming Liu4, Yu-Ling Gan2
1Institute of Brain Science, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Neurology
|June 1, 2026
Summary
This study identified a novel genetic risk locus on chromosome 19p13.12 associated with early-onset ischemic stroke (IS) in the Han Chinese population. It also revealed rare pathogenic variants contributing to distinct genetic architectures in East Asian early-onset stroke.
Area of Science:
- Genetics
- Neurology
- Precision Medicine
Background:
- Genome-wide association studies (GWASs) have identified common genetic risk loci for ischemic stroke (IS), primarily in European populations older than 55 years.
- Limited understanding exists regarding genetic risk variants for early-onset IS (ages 18-54) in East Asian populations.
Purpose of the Study:
- To identify common and rare genetic risk variants associated with early-onset IS in Taiwan.
- To investigate the functional relevance and genetic architecture of IS in Han Chinese individuals.
Main Methods:
- Conducted GWASs of early-onset and all IS cases against stroke-free controls from the Taiwan Precision Medicine Initiative.
- Performed fine-mapping, linkage disequilibrium analysis, phenotype correlations, phenome-wide association studies (PheWASs), and pathway enrichment analysis.
- Examined rare pathogenic variants using whole-exome sequencing in early-onset sporadic and familial stroke probands.
Main Results:
- Identified a novel risk locus at chromosome 19p13.12, significantly associated with early-onset IS (lead SNP rs541118668 in CYP4F3).
- This locus and six others were associated with all IS cases in East Asians.
- Novel SNPs were linked to the small vessel occlusion (SVO) subtype; PheWASs confirmed associations with cerebrovascular diseases.
- Discovered likely pathogenic variants in 15.6% of early-onset IS probands, particularly those with SVO and cerebral venous infarction.
Conclusions:
- Identified a novel, age-specific genetic hotspot for IS at chromosome 19p13.12 in Han Chinese.
- Findings reveal a distinct genetic architecture underlying early-onset stroke in East Asians, involving both common and rare variants.
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