ABSTRACT
The completion of the human genome project1
should now enhance our ability to understand the interplay between genetics and environment in the pathogenesis of many common chronic diseases, including stroke, and to develop new approaches to disease prevention. There are four principal lines of evidence supporting a genetic contribution to stroke risk. First, there are numerous monogenetic disorders associated with stroke, including the recently described disorder cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)2. These conditions are considered simple Mendelian traits because they exhibit a dominant or recessive inheritance pattern attributable to a single gene3. Second, studies of human populations have shown strong evidence for the familial aggregation of stroke4. Since it is common for stroke to run in families but dominant or recessive modes of inheritance are uncommon, these studies have supported a complex (unknown) mode of inheritance or a role for a shared environment. Third, twin studies have shown concordance rates of 3.6% for dizygotic twins and 17.7% for monozygotic twins5, suggesting a genetic basis for the familial aggregation. Fourth, candidate gene studies have been increasingly productive. For example, studies of the stroke-prone spontaneously hypertensive
rat have shown the existence of a blood pressure-independent single gene locus predisposing to stroke6; the same locus has been demonstrated to be associated with ischemic stroke in human populations7.
