Genetic Approaches to Coronary Heart Disease Review Article

Developments in high-throughput genotyping have progressed to the point where genome-wide association studies are becoming practical. Multistage designs involving large numbers of sequence variants (not, vert, similar300,000) and relatively large samples sizes (several hundred cases and control subjects) will be essential to reliably detect alleles with appreciable effect sizes (2-fold increase in relative risk). Direct sequencing of candidate genes in cases and control subjects provides an alternative approach that can reveal low-frequency alleles that influence disease susceptibility. Ultimately, the outcome of both approaches will depend on the genetic architecture of coronary heart disease.