conserved nucleotides and deficit in CNCs is probably due to the fact that the majority of the signal for conserved nucleotide comes from exonic sequences that are close to the TSS where the associations are mainly found. The deficit of associated SNPs in CNC sequences is somewhat surprising because previous studies have suggested that they are selectively constrained 31,33,34 and in some cases have been shown to play a role in gene regulation 35-37. It is possible that the skew toward large effect sizes also skews the distribution of causal regulatory variants.
