Our combined model at age 50 identified BDNF (rs7103411) and FTO (rs1558902) variants, along with metabolic parameters such as low D5D enzyme activity, high levels of 20:5n-3 in serum CE, FBG, AST, apoB, and low serum HDL-C levels, as significant risk factors for MetS at age 70 in men. Here, BDNF is linked to metabolic syndrome.