Interaction of genetic variants and DNA methylation at CpG sites can influence an individual’s vulnerability to disease. Single nucleotide polymorphisms (SNPs) can affect gene expression or function via mechanisms that are ultimately epigenetic by introducing or removing CpG dinucleotides (that then may or may not be sites of methylation). These are called CpG-SNPs. The two different parentally derived alleles can exhibit different methylation patterns; this is called allele-specific DNA methylation (ASM).42,43 A genome-wide survey showed that a significant proportion (38–88%) of ASM regions are dependent on the presence of heterozygous SNPs in CpG dinucleotides that can either lead to or disrupt their methylation potential.44 SNPs can also influence DNA methylation across extended genomic regions. These SNPs are referred to as methylation quantitative trait loci (mQTLs). The strength of the association between SNPs and CpGs tends to decrease as the distance between them increases.45 Two recent studies identified AUD-associated CpG-SNPs46 or mQTLs.45
