which covers more than 850K CpGs across the genome. Additionally, whole genome bisulfite sequencing (WGBS) (or bisulfite treatment of DNA followed by high-throughput sequencing) has been shown to be an important method for studying DNA methylation at single-base resolution,93 and it has been applied to study epigenetic regulation mechanisms of diseases such as cancer.94 However, WGBS is costly and genetic or epigenetic studies of psychiatric disorders (such as AUDs) usually require analyzing the data from a large sample (considering that genetic and epigenetic marks may exert a minor or moderate effect on psychiatric disorders). With the decline of the DNA sequencing cost, it is expected that WGBS should be applied more widely in DNA methylomic studies of AUDs or other complex disorders, if appropriate funding becomes available. For example, the Reduced Representation Bisulfite Sequencing (RRBS) method developed by Diagenode (www.diagenode.com) is a cost-effective and high throughput approach, and it provides improved coverage of up to four million CpGs for the human genome.
