Systematic review of methods and results of studies of the genetic epidemiology of ischemic stroke

To design appropriate molecular genetic studies, we first need to understand the genetic epidemiology of stroke. We therefore performed a systematic review of the literature to assess the heritability of stroke according to methodological quality of studies and to determine any heterogeneity in findings between studies and possible publication bias. We searched for twin studies and studies of family history of stroke using bibliographic databases and by hand-searching reference lists and journals. Odds ratios (ORs) for family history as a risk factor for stroke were calculated within studies and combined by meta-analysis. Heterogeneity between studies, methodological quality of studies, and the influence of the age at which stroke occurred in both probands and relatives were assessed. We identified 53 independent studies (3 twin, 33 case-control, and 17 cohort). Monozygotic twins were more likely to be concordant than dizygotic twins (OR, 1.65; 95% CI, 1.2 to 2.3; P=0.003). A positive family history was a risk factor for stroke in both case-control (OR, 1.76; 95% CI, 1.7 to 1.9; P