A GWAS for a disease is usually a variant of a cross-sectional case-control study, the study design that is the familiar workhorse in biomedicine and epidemiology (Schlesselman, 1982). Another term for GWAS is whole-genome association study (WGAS, “dŭb’ əl-yōō găs”). Cases are defined as individuals who meet lifetime criteria for a disease (e.g., Crohn’s disease, type 2 diabetes mellitus, or schizophrenia). Controls should have never met criteria for the disease and, ideally, be through the period of risk. Moreover, for case-control comparisons to be as unbiased as possible, controls should be draws from the same population as cases particularly with respect to exposure to any potentially relevant risk factors (Rothman, 1986). Each individual in the sample is assayed (i.e., genotyped) for a comprehensive set of genetic markers scattered across the genome. The genetic markers are single nucleotide polymorphisms (SNPs, “snips”) which are relatively straight-forward to assay. The two major current GWAS technological platforms contain 906,000 (Affymetrix 6.0) and 1,199,187 SNPs (Illumina 1M) spaced across the 22 autosomes (chr1–chr22), the sex chromosomes (chrX and chrY) and the mitochondrial genome (chrM).
