Sex differences in the effect of APOE-ε4 on AD risk and on AD endophenotypes are well-established.3, 14 Therefore, we performed post hoc analyses examining the possible modifying effects of both sex and APOE-ε4 for the four X-linked genes (MCF2, HDAC8, SLC10A, and FTX) by leveraging a three-way interaction model. The gene discussed is HDAC8; the disease is Alzheimer disease.