Whole-genome sequencing reveals new Alzheimer’s disease-associated rare variants - Rudy Tanzi, Lars Bertram and Win Hide

Here we report the results of a family-based whole-genome sequencing (WGS) rare-variant association study in 2,247 subjects from 605 multiplex Alzheimer's disease (AD) families, followed by replication analyses in an independent case-control cohort comprising of more than 1,650 individuals. Employing both single-variant and spatial clustering-based (“region-based”) testing, we identified 13 new AD candidate loci (4 from single-variant, 9 from spatial-clustering analyses) that yield consistent rare-variant signals in both discovery and replication cohorts.