This includes burden rare variant signals in genes with variants previously associated with AD, such as ABCA7, PILRA, SORL1, TREM2, as well as novel genes, such as ZNF655. Recently, we have performed a rare variant region-based analysis in whole-genome sequencing (WGS) data [19] using a family-based design and a burden family-based association test (FBAT), which was based on estimating the correlation between rare variants based on the observed empirical distribution [20]. The gene discussed is TREM2; the disease is Alzheimer disease.