That there is an effect of the MTHFD1L variant but not of the MTHFR is in line with findings of the genome-wide mega-analysis on major depressive disorder by Ripke and colleagues,39 where the index SNP of the MTHFD1L gene (SNP with the highest significance) showed a more significant association (rs563440; P=0.004) with major depression than the index SNP from MTHFR (rs17037425; P=0.079). Here, MTHFR is linked to major depressive disorder.