Mendelian randomization offers a powerful tool to understand causality, particularly for an intermediate phenotype that is controlled by a genetic alternation of relatively strong effect.10 Mounting evidence indicates a close relation between circulating homocysteine concentrations and an exonic polymorphism, C677T, in methylenetetrahytrofolate reductase (MTHFR) gene, with carriers of 677T allele having elevated homocysteine concentrations.11, 12, 13 However, the implication of long‐term genetically elevated homocysteine concentrations in the development of DKD has not yet been clarified. This evidence concerns the gene MTHFR and diabetic kidney disease.