APOE and Alzheimer disease: The success of the APOE case-control association design led to more studies such as the rare variant association studies (Kamboh, 2018), small samples of whole exome sequence (WES) studies (Guerreiro et al., 2013), Large GWAS of common variants (Kunkle et al., 2019; Andrews et al., 2020), as well as the large-scale sequencing efforts like the Alzheimer’s Disease Sequencing Project (ADSP) (Beecham et al., 2017) which have all implicated dozens of loci but do not implicate the FAD genes.