It is also noted that the gene encoding DNMT3L is located on Chromosome 21; given the previous report of an average DNA methylation age acceleration of 6.6 yr in blood and brain tissue in individuals with Down syndrome (Horvath et al. 2015) and the role of DNMT3L in stimulating DNMT3A de novo methylation, further investigations are needed to explore the potential relevance of this observation. Here, DNMT3A is linked to Down syndrome.