While we have concentrated on genotype variation in our discussion of molecular genetic studies of sex differences in psychiatric phenotypes, other “omics” domains may also play a role. Modifications, such as DNA methylation may have an impact on sex differences. In fact, Maschietto and colleagues 129 postulated that a primary driver of sex differences in neuropsychiatric disorders is differential DNA methylation of autosomes by sex. The majority of the work in this area has been conducted in rodents, where it has been showed that DNA methylation plays a role in establishing sex differences in the brain during development, while profiles of epigenetic changes by sex during brain development in humans are not yet readily available. 130 Differential gene expression patterns have been reported in male and female postmortem brain tissue, although it is unclear whether the expression and methylation differences result from, or are in the etiologic pathway of neuropsychiatric disorders. 131 Recently, Xia and colleagues 132 investigated the contribution of DNA methylation to sex differences in psychiatric disorders, and reported thousands of sex‐differentially methylated positions (DMPs) and regions (DMRs).
