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. This evidence concerns the gene TMEM106B and Alzheimer disease.