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Although Alzheimer disease (AD) shows strong patterns of heritability, uncommon variants in three genes (APP, PSEN1, and PSEN2) account for only a small percent of AD cases (i.e., early-onset autosomal dominant disease) — and the association of the APOE genotype with development of late-onset AD does not fully account for the excess risk for disease in first-degree relatives of AD patients. In a pair of genome-wide association studies, both of which were conducted in three stages (initial identification of susceptibility variants followed by two stages of testing for associations with AD risk), researchers sought to identify other susceptibility loci.
The first study was specific to late-onset AD. Overall, pooled data were analyzed from 12 c…