APOE and early-onset autosomal dominant Alzheimer disease: GWAS are designed to identify disease variants of relatively high frequency (MAF >1%) in a population operating under the common disease/common variant hypothesis.38 In PD, most identified risk factors have an odds ratio (OR) between 0.8 and 1.5.39 Similarly, in Alzheimer disease—apart from APOE (OR ∼4)—common genetic risk factors have low ORs ranging from 0.8 to 1.2.