We were able to successfully validate the previously reported association of APOE ε4 with Alzheimer's disease [18] (rs429358, P = 3.41 × 10−9, OR = 3.59) in our initial WES screening stage (Fig. 1B and Supplementary Table S1), suggesting the reliability of the current extreme phenotype sampling approach. Here, APOE is linked to early-onset autosomal dominant Alzheimer disease.