As compared to candidate gene studies, genome-wide association studies (GWAS) have the advantage of covering the entire genome in an hypothesis-free way, and the methodology is powerful for detecting relatively common alleles (minor allele frequency [MAF] >5%) of moderate effect. As discussed later, the impact of less common variants cannot be studied by using the current GWAS arrays and requires sequencing strategies. Another advantage of GWAS is that the same genotyping arrays are obtained in different samples facilitating the combination of results from different studies in meta-analyses. This is a crucial aspect because extremely large study samples are necessary to be able to detect the small effects of many common variant on complex diseases. Of note in GWAS, up to 5 million SNPs can be simultaneously tested raising the issue of false positives due to multiple testing. To achieve an effective P value of .05, the genome-wide significance threshold is usually set at approximately 10−8.
