Of the 16 single variants outside the APOE region tested in the replication samples (Table 2, Supplementary Table S3), the TREM2 R47H mutation and four variants in three other previously known genes (one missense and one synonymous variant in MS4A6A, a synonymous variant in PILRA, and a missense variant in CR1) were significantly associated with AD in the combined discovery and replication analysis (Table 2). This evidence concerns the gene APOE and Alzheimer disease.