Figure 2.

Interpreting positive GWAS signals. (a) GWAS can point to chromosomal loci that may harbor causal variants. (b) The associated SNP will act as a marker of multiple additional common variants in an LD block. The marker SNP or any of these other common variants could be the causal variant. The very low odds ratio across the population might represent a tiny effect of one of these variants in every individual or a large effect that arises only in the context of some rare mutation. (c) Alternatively, at least some common SNP signals could actually be tagging rare variants of large effect in the population, which are in strong LD with it (stars). If these occur, by chance, more prevalently on one haplotype than on another, this will lead to a slightly increased frequency of one allele in cases when compared to controls (that is, an association signal).