Genomewide significant SNPs on chromosome 10 were not in linkage disequilibrium (r2 ≥ 0.6) with non-synonymous variants in neighboring genes. No significant cis-eQTLs were identified for any chromosome 10 variant in any tissue in GTEx (43) as well as dorsolateral prefrontal cortex (dlPFC) tissue from the Common Mind Consortium data(44). However, there was preliminary evidence that rs1409568 (RegulomeDB score 3a), but not other variants in the region (scores ≥ 5) may have regulatory effects (45). Closer inspection in the Epigenome Browser (46) showed that rs1409568 was accompanied by enhancer-enriched active histone modifications (H3K4me1 and H3K27ac) in a variety of brain tissues (Figure 2). Evidence of an active enhancer was particularly prominent in the dorsolateral prefrontal cortex (dlPFC), angular gyrus, cingulate gyrus and the inferior temporal lobe. There were also enriched H3K4me1 and H3K27ac signals in the middle hippocampus and the substantia nigra, however these signals were not detected at corrected thresholds defined by MACS (q-value cutoff 0.05). All of these regions are strongly implicated in the etiology of addiction (47).
