Figure 3.

Interactions Impacting the Expression of CPEB4 May Represent Haplotype Effects

(A) A significant interaction between rs6864691 and rs969518 regulating the expression of CPEB4 was identified. The cis-eQTL rs72812817 mediated this interaction in the conditional analysis; however, none of these variants were within putative regulatory elements in GM12878 assayed by the ENCODE Project.

(B) However, a D′ heatmap of the region (the numbers correspond to SNP labels in A) illustrated that an indel, rs144869372, always occurred on the background of the cis-eQTL (D′ = 1).

(C) This occurs despite modest r² values, as shown in the r² heatmap of the region. There is evidence from ENCODE (A) suggesting the indel may be functional, as it occurs within both a ChromHMM strong enhancer (yellow) and a CTCF binding peak in GM12878.

(D) Notably, the indel is predicted to alter the binding of CTCF by HaploReg, by altering the last three nucleotides in the binding motif. Given the functional genomics evidence, the indel may be the causal variant and is detected by interactions that tag the haplotype carrying the indel.