The exact etiology of ischemic stroke remains unclear, because multiple genetic predispositions and environmental risk factors may be involved, and their interactions dictate the complexity. Family-based studies provide unique features in design because of their robustness to population admixture and stratification. The Fangshan / Family-based Ischemic Stroke Study In China (FISSIC) program aims to conduct a genetic pedigree study of ischemic stroke in rural communities of China.

The FISSIC program is a community-based and hospital-centered genetic epidemiological study of ischemic stroke. The study design has two components: first, a family-based study of ischemic stroke pedigrees, including probands, their siblings, and their parents; second, the traditional matched case-control study of ischemic stroke cases and their unaffected spouses. Cases with confirmed ischemic stroke are included as probands; after their informed consent is obtained, their parents, siblings, and unaffected spouses are recruited and screened by using the proband-initiated contact method. Stroke status is verified at the central hospital, and the index stroke for each case is subtyped by medical records. Baseline clinical and demographic data are collected by questionnaire, and longitudinal follow-up visits are scheduled. Blood samples are collected from all enrolled participants through the three-tier prevention and health care network (village, township and county level) in the study area. The samples are sent to the central laboratory for processing, testing, and genotyping. The genotype data are then merged with the clinical, environmental, and follow-up data for analysis. Comprehensive statistical methods are applied to both family-based and case-control data to ascertain potential complex genetic and environmental factors and their interactions.

Inclusion Criteria:

• Diagnosis of at least one ischemic stroke confirmed by the study neurologist on the basis of history, medical records, and head imaging by CT or MRI;
• At least 18 years old by the time of enrolment in the study;
• At least one full sibling or parent alive in areas nearby;
• Written informed consent by the patient or surrogate.

Exclusion Criteria:

• Diagnosis of Transient Ischemic Attack (TIA) only;
• Diagnosis of vasospasm after subarachnoid hemorrhage;
• Diagnosis of some Mendelian disorders: CADASIL, Fabry disease, MELAS, or sickle cell anaemia;
• Diagnosis of iatrogenic ischemic stroke associated with a surgical / interventional procedure such as coronary artery bypass grafting, carotid endarterectomy, or heart valve surgery;
• Diagnosis of ischemic stroke associated with autoimmune condition or endocarditis.

Ischemic stroke probands will be enrolled in two parts: incident cases from primary care clinic and prevalent cases from communities, and their family members will be recuited in communities.