Genetic loci associated with Alzheimer's disease.

The article by Lambert et al. reports the identification of 11 novel susceptibility loci for late-onset Alzheimer's disease. The observations of this study significantly enhance the field since they further disentangle the genetic causes and pathways underlying Alzheimer's disease by identifying novel disease-associated variants clustering in specific pathways. These pathways include APP processing, lipid metabolism, inflammation/immune response, intracellular trafficking/endocytosis, tau metabolism, synaptic function. All of the newly identified disease-associated variants have small effect sizes with increases in risk of 10-20%. The cumulative population attributable fraction associated with known genetic variants amounts now to approximately 80%. This article also underlines the ongoing value of genome-wide association studies for identification of causative common variants in the era of whole-exome and whole-genome sequencing studies.