variants in APP and TREM2 were found to confer strong protection or elevated risk of LOAD (Guerreiro et al., 2013; Jonsson et al., 2012; Jonsson et al., 2013). However, the overall contribution of these new common and low-frequency variants to the heritability of LOAD is very small, suggesting that a large fraction of the genetic variance beyond the APOE risk still remains hidden. Can we clarify the pathology of LOAD by zooming out to the pathway level to search for emergent risk of many genomic contributions? If so, how can we identify the key causal genes in these pathways?
