Rs6265 is in a protein-coding region of the gene, may alter BDNF protein function and one study reported that the Met allele was associated with increased protein concentrations.53 However, polymorphisms in other regions, including promoter or intronic regions, have also been shown to affect gene regulation, demonstrating that physical proximity is not essential.54, 55 Further investigation of the role of BDNF genetic variation in influencing the association between methylation levels and depression (Supplementary Figure S5) is required. Here, BDNF is linked to depressive disorder.