Genetic Association Studies and Next Generation Sequencing in Stroke: Methods

Although some forms of stroke are inherited in a Mendelian manner, being caused by a single genetic locus of strong effect, most strokes are sporadic and, like other complex diseases such as asthma and diabetes mellitus, have a genetic component that is complex and involves multiple loci of modest effect. Controversy surrounds whether these genetic variants are likely to be common (>1–5% prevalence) across most populations, each with very small effect sizes (the so-called common disease-common variant hypothesis), or whether these variants are likely to be rare (<1%), perhaps even unique to families or individuals, with larger effect sizes (the so-called common disease-rare variant hypothesis). In either case, a common approach over the last 15 years has been to test for association between common genetic variants and stroke using traditional population-based designs such as case-control and cohort studies.