Detection of common single nucleotide polymorphisms synthesizing quantitative trait association of rarer causal variants

Probability distribution of the QT value within subgroups classified by marker SNP genotypes. (A) In the whole population, the total QT distribution (gray curve) comprises a mixture of normal distributions (black curves) with unit variance and the mean 0, 1, or 2, which correspond to genotypes b₁/b₁, B₁/b₁, and B₁/B₁ at the causal variant. As genotype B₁/B₁ is rare (0.25%), the corresponding curve appears flat. (B) QT distribution among individuals with A/A genotype at the marker. As B₁/B₁ and B₁/b₁ genotypes are enriched in this subgroup due to LD, the variance is enlarged, as noticeable from the lower peak and wider distribution of the gray curve. (C) Individuals with the A/a genotype have either genotypes b₁/b₁ or B₁/b₁, and the QT variance is moderately enlarged. (D) All individuals with a/a genotype at the marker have b₁/b₁ genotype at the causal variant. The QT variance is 1.10 in A, 1.38 in B, 1.19 in C, and 1 in D.