The presence of LD creates two possible positive outcomes from a genetic association study. In the first outcome, the SNP influencing a biological system that ultimately leads to the phenotype is directly genotyped in the study and found to be statistically associated with the trait. This is referred to as a direct association, and the genotyped SNP is sometimes referred to as the functional SNP. The second possibility is that the influential SNP is not directly typed, but instead a tag SNP in high LD with the influential SNP is typed and statistically associated to the phenotype (figure 3). This is referred to as an indirect association [10]. Because of these two possibilities, a significant SNP association from a GWAS should not be assumed as the causal variant and may require additional studies to map the precise location of the influential SNP.
