Fig 3.

Genome-wide association study (GWAS) design. A typical cancer GWAS starts with the selection of a large number of individuals affected with a specific type of cancer and a suitable comparison group without cancer. DNA is isolated from each individual and genotyped using commercially available genome platforms (ie, chips) that assess for common genetic variations in the form of single nucleotide polymorphisms (SNPs) across the entire human genome. Data are reviewed to ensure appropriate genotyping quality. In phase I, stringent statistical methods are used to assess for associations between SNPs passing quality thresholds and cancer risk. In phase II, SNPs found to be significantly associated with cancer risk (approximately 5% to 10% of all SNPs) are tested in a larger set of independent patients and controls using arrays containing the putative SNPs of interest. Some studies proceed to further evaluation of putative SNPs in a third phase using larger and more heterogeneous populations to confirm the genotype associations.