The pleiotropy analysis also revealed that 4 (BIN1, HLA, PICALM, and APOE) of the 25 previously reported GWS AD risk loci [7, 19–21] were at least one order of magnitude more significantly associated with the joint model of NP + NFT than each of these traits analyzed separately, suggesting that these genes are involved in pathways leading to both plaques and tangles [22–25]. The gene discussed is APOE; the disease is Alzheimer disease.