APOE and Alzheimer disease: We observed strong evidence APOE ε4 interaction (interaction β = −0.239, p = 1.26 × 10−6, q = 4.86 × 10−3), with negligible mean genetic effects in ε4 non-carriers (main effect p = 0.682) but progressively stronger suppression in ε4 heterozygotes and homozygotes (Figure 3d), suggesting that the variant exacerbates TMEM106B deficiency specifically in the APOE ε4 background, which itself confers AD risk.