Genome-wide association studies: a primer.

Statistical power in a GWAS.Figure 1 illustrates statistical power for GWAS of four different sample sizes assuming a discrete trait with lifetime prevalence of 0.01 (similar to schizophrenia, bipolar disorder, or anorexia nervosa), a log additive genetic model, a genotypic relative risk of 1.25 (typical for GWAS for human complex diseases, and two-tailed α=5×10−8). The x-axis shows minor allele frequency and the y-axis statistical power

Properties of GWAS findings from the literature.Figure 2a shows quarterly temporal trends in the publication of GWAS. Figure 2b shows the accumulated GWAS literature on human diseases. The x-axis if the population prevalence of a risk variant and the y-axis the relative risk conferred (both using a log10 scale in order to provide separation). The grey point show the prevalence-risk combination for all SNP associations for human complex diseases with p < 5×10−8. Power curves are shown for 1,000 cases/1,000 controls (red line) and 25,000 cases/25,000 controls (green line). The blue lines depict the 10th–90th percentiles from the GWAS literature for allele frequency (horizontal line) and relative risk (vertical line). The intersection of the blue lines is the median population prevalence (0.3) and relative risk (1.25).

Images important for assessing a GWAS.See text for description. These figures are from different studies. Figure 3a shows the allele intensity plots for two SNPs from which SNP genotype calls are generated. Figure 3b depicts a quantile-quantile plot in which the observed p-values are plotted against the p-value distribution expected by chance (on –log10 scale). Figure 3c shows a Manhattan plot. Figure 3d shows an expanded set of findings in the region of neuregulin 1 (NRG1).