Genetic factors play an important part in the development of Alzheimer’s disease. In autosomal dominant Alzheimer’s disease, highly penetrant mutations in APP, PSEN1, or PSEN2 result in monogenic Alzheimer’s disease, typically with early onset.3 However, most cases of Alzheimer’s disease (99%) involve multiple genetic, environ mental, and lifestyle factors, with genetics accounting for up to 53% of total phenotypic variance.4 Until 2018, the largest genome–wide association study (GWAS) of Alzheimer’s disease had been done in 2013, identifying 19 risk loci.5 Beyond locus identification, characterization of risk loci can implicate functional genetic variants and genes, which can inform mechanistic studies and rational drug development. Compared with drug targets with no evidence of genetic association, drug targets supported by evidence of both genetic association with disease and functional data are twice as likely to progress from phase 1 studies to successful approval.6
