Assessment of Key Genetic vaRianTs and thEir iMpacts In Stroke
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 1,000
- 试验地点
- 11
- 主要终点
- Prevalence of stroke-related genetic polymorphisms measured by whole genome sequencing (WGS)
研究概览
简要总结
Stroke is the leading cause of death and disability in Brazil and worldwide, with a significant socioeconomic impact. Despite advances in prevention and treatment, the role of genetic variants in ischemic stroke remains underexplored, especially in genetically diverse populations like Brazil's. International studies such as MEGASTROKE and GIGASTROKE have identified risk loci for stroke, but with low representation of the Latin American population. This study aims to fill that gap by evaluating the prevalence and clinical impact of genetic polymorphisms previously described in Brazilians, thereby laying the groundwork for precision medicine within Brazil's Unified Health System (SUS).
详细描述
Study Overview: ÁRTEMIS-Brazil is a multicenter, case-control study that will recruit 1,000 participants (500 stroke patients and 500 controls) across 10 hospitals in Brazil. All participants will be extensively phenotyped, including demographic, clinical, lifestyle, neuroimaging, and laboratory data, in order to create a comprehensive dataset that links genomic information with health outcomes. Peripheral blood samples will be collected and processed under strict biobanking standards. DNA will undergo whole genome sequencing (WGS), enabling high-resolution investigation of genetic variation in an admixed population.
2) Genomic and Bioinformatics Methodology: The analytical workflow has been designed to ensure high-quality, reproducible results and includes the following components: Pre-processing Removal of adapters, low-quality bases, and contaminant sequences. Filtering of reads based on Phred quality scores to retain only high-confidence sequences.
Alignment and Assembly Mapping of cleaned reads to the human reference genome (GRCh38). Evaluation of coverage, depth, and mapping accuracy. Quality metrics will be benchmarked against international standards.
Variant Analysis Identification and annotation of genetic variants, including single nucleotide polymorphisms (SNPs) and insertions/deletions (indels).
Annotation pipelines (e.g., GATK, ANNOVAR, VEP) will classify variants by predicted functional effect, population frequency, and pathogenicity.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age ≥18 years;
- •Confirmed diagnosis by neuroimaging (CT or MRI) of a first episode of ischemic stroke in the last 12 months;
- •TOAST classification of stroke available: cardioembolic, lacunar, atherosclerotic, or undetermined due to the presence of multiple sources (cardioembolic/atherosclerotic);
- •Modified Rankin Scale (mRS) ≤4 at the time of inclusion;
- •Ability and willingness to provide consent and participate in follow-up assessments.
- •Age ≥18 years;
- •Reside in the same household or, if not, in the same neighborhood as the case group participant;
- •Not be a blood relative of the case group participant;
- •Ability and willingness to provide consent and participate in follow-up assessments.
排除标准
- •Ischemic stroke with a distinct etiology based on TOAST criteria (e.g., infectious, autoimmune, endocarditis, reversible cerebral vasoconstriction syndrome, drug-related causes);
- •Diagnosis of monogenic or mitochondrial disorders, such as CADASIL, Fabry disease, homocystinuria, MELAS, sickle cell disease, among others;
- •Clinical conditions that reduce life expectancy to less than one year (e.g., neoplasia);
- •Inability to undergo magnetic resonance imaging (due to metal artifacts, MRI-incompatible implants, claustrophobia);
- •Other conditions that, at the investigator's discretion, prevent participation or compromise follow-up.
- •Personal history of stroke, transient ischemic attack (TIA), coronary, or peripheral artery disease;
- •Serious comorbidities that may impact participation or confound the results;
- •Clinical conditions that reduce life expectancy to less than one year;
- •Inability to provide consent due to cognitive impairment or other factors;
- •Inability to undergo magnetic resonance imaging (due to metal artifacts, incompatible implants, claustrophobia);
- •Diagnosis of monogenic or mitochondrial disorders, such as CADASIL, Fabry disease, homocystinuria, MELAS, or sickle cell disease;
- •Other conditions that, at the investigator's discretion, prevent participation or compromise follow-up.
结局指标
主要结局
Prevalence of stroke-related genetic polymorphisms measured by whole genome sequencing (WGS)
时间窗: 60 months
Frequency and distribution of single nucleotide polymorphisms (SNPs) and small insertions/deletions (indels) previously associated with stroke, identified from whole genome sequencing data. Frequencies will be compared with international genomic databases to evaluate similarities and differences in an admixed Brazilian population. Unit of Measure: Percentage of participants carrying the variant; allele frequency (%).
Genetic ancestry composition assessed by whole genome sequencing (WGS)
时间窗: 60 months
Proportion of ancestry components (e.g., European, African, Indigenous American) estimated from population-specific genetic markers using WGS. Comparison between stroke cases and controls will be performed to explore associations with stroke risk. Unit of Measure: Proportion of ancestry components (%).
Pharmacogenetic variants associated with drug metabolism identified by whole genome sequencing (WGS)
时间窗: 60 months
Prevalence of variants in pharmacogenes (e.g., CYP450 genes, platelet receptor genes, anticoagulant metabolism pathways) assessed through WGS. Results will be compared with reference databases and analyzed in stroke cases and controls. Unit of Measure: Percentage of participants carrying pharmacogenetically relevant variants; allele frequency (%).
次要结局
未报告次要终点