One rare variant in the complement C7 gene, rs3792646, leading to the missense mutant p.K420Q with a predicted damaging effect (Combined Annotation-Dependent Depletion score = 20.3) [49], was the only exome-wide significant hit showing an association with susceptibility to Alzheimer's disease (P = 1.09 × 10−6, OR = 7.853, Fisher's exact test; Fig. 1B, Table 1 and Supplementary Table S1), with the exception of APOE rs429358. This evidence concerns the gene APOE and early-onset autosomal dominant Alzheimer disease.