ability to draw direct correlations. Nonetheless, genome-wide QTL comparisons in human brain have shown that almost half of SNPs that act as both an eQTL and meQTL show the same direction of association for DNAm and RNAexp,41 as we observed here for DNMT3B and before for CHRNA5.42 The previously established nicotinic acetylcholine receptor genes also harbor nicotine dependence-associated SNPs with important consequences for gene regulation, including noncoding SNPs that correlate with DNAm,42 splicing,23 and/or RNAexp43, 44 in brain tissues that are frequently studied for nicotine and other SUDs because of their role in primary reward pathways and executive function, such as prefrontal cortex.45 This newly identified DNMT3B SNP association highlights changes in DNAm in fetal brain and with RNAexp specifically in cerebellum, a part of the brain that has often been overlooked despite some indications for its involvement in the neurobiology of addiction.46–48
