Genetic Approaches to Coronary Heart Disease

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 (∼300,000) 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.