The WashU EpiGenome Browser (http://epigenomegateway.wustl.edu/browser/; Zhou et al., 2011, 2013, in press) was used to annotate the epigenetic landscape surrounding rs604300. As described in detail in the Supplement, we found evidence that this SNP resides just downstream of epigenetic histone modifications (i.e., H3K4me1, H3K27ac) within a functional enhancer that likely upregulates gene expression. There was evidence of tissue specificity wherein enrichment is highest in neural tissue. Moreover, there was evidence that methylation and histone modification in this epigenetically-regulated enhancer region of MGLL may play role in MGLL transcription (Figure 5 Figure S8). As such, it is possible that environmentally-mediated individual differences in methylation and histone modification-related enhancement of this region may produce differential MGLL expression in the brain. Rs604300 is located near this epigenetically-regulated enhancer; while we are unable to test for genotype-dependent differences in methylation and histone modification with the data available to us, this annotation suggests that rs604300 genotype itself or a SNP in LD with it may impact MGLL expression by affecting epigenetic modification within this MGLL enhancer.
