To investigate the mechanisms of how DNA methylation regulates gene transcription, we must first understand the various biological influences on DNA methylation. Demographic factors, such as sex,76 age,77 and ethnicity,52,78 are known to impact or correlate with DNA methylation. DNA methylation patterns can also be influenced by various environmental exposures, including pre- and post-natal nutrition,79–81 early life stress,82–84 psychosocial stress,85,86 and inflammation.87 Additionally, genetic variants (or mQTLs) can dramatically alter methylation levels of nearby CpGs. mQTLs are widely dispersed throughout the genome across different tissues.43,88–91 Three studies have examined the effect of genetic variants on methylation of proximal CpGs in AUD subjects. Philibert et al.68 investigated the association between genotypes of the variable number tandem repeat (VNTR) polymorphism in the promoter region of MAOA and the overall methylation level of the MAOA promoter region using lymphoblastoid cell lines derived from blood lymphocytes of 191 subjects at high risk for AUDs. They reported that women homozygous for the 3,3 allele of the VNTR polymorphism had a trend (p <0.10) of increased overall methylation of the MAOA promoter region than women homozygous
