Only two studies have examined the exons of the loci considered here with the goal of identifying causal variants for AD in subjects of European ancestry, to our knowledge. These studies also found that single, common variants are not causal (Vrieze et al., 2014, Zuo et al., 2013a). Only the Vrieze et al. study examined if a variant set was associated with AD. The sets they examined, non-synonymous rare variants, were not significantly associated with AD. This is equivalent to our non-synonymous rare variant findings which is unsurprising given that the MTFS is a subset of the subjects in the Vrieze et al. study. As these previous studies focused only on exons, they would have missed 65 out of 73 (89.1%) variant set findings with p-value < 0.05 found outside protein coding regions. To our knowledge, no previous investigation has examined the role regulatory variant sets may play in AD.
