Although no heterogenous variants were revealed in the scatter plot (Figure 3) and leave-one-out analysis (Figure 4), the causal estimates given by Wald ratios from both rs3195944 (OR = 1.25; 95% CI, 1.06–1.48; p = 0.007) and rs1227731 (OR = 1.26; 95% CI, 1.08–1.46; p = 0.003) were notably nominally significant (p < 0.05) when examining the effect of GDF-15 on AD mediated by individual SNP (Supplementary Table 5). Here, GDF15 is linked to Alzheimer disease.