role of variation in PER2 suggest that SNP rs56013859 may alter the binding motives for transcription factors Sp1, c-myb, and nuclear factor B, suggesting a possible regulatory function of this SNP in transcriptional activation of PER2 [11]. However, one limitation of this study is that we did not find any allele-specific expression of Per2 in peripheral blood from IMAGEN participants or on publicly available eQTL browsers of cortical tissue. Since there is distinct temporal variation and pronounced expression differences of Per2 across the life span (Figure 2) indicating temporal and regional-specific regulatory mechanisms, these results do not rule out a role of SNP rs56013859 or perhaps rare or intermediate variants in linkage disequilibrium with this SNP in transcriptional regulation. Recently, Agapito et al. [36] demonstrated a PER2 mutation in mice to be associated with the regulation of β-endorphin release to acute and chronic ethanol challenges, providing another clue to the mechanism of different effectiveness of alcohol drinking as a means to cope with life events.
