Genome-wide studies identify disease-associated alleles. (a) GWASs compare the allelic frequencies of SNPs across the entire genome in case and control populations. A statistically significant difference in the allelic frequencies between cases and controls constitutes an association with disease. In this example, a guanine (G) at SNP2 is associated with the disease. (b) Only a fraction of all known SNPs that are sufficient to tag haplotypes (gray and dashed boxes) are genotyped. The actual causal allele can be another SNP (yellow circle) in the same haplotype block. In the example, the SNP might not be a non-coding variation affecting expression of the gene shown at the top left. Experimental evidence can be used to identify regulatory sequences that harbor SNPs and that are thus likely to have a role in the disease, as illustrated by the H3K27ac and H3K4me1 signals. Functional tests of the candidate sequences spanning the putative disease SNP are performed to identify allelic-specific effects on gene expression using reporter genes.
Sakabe et al. Genome Biology 2012 13:238 doi:10.1186/gb-2012-13-1-238