Figure 5.

Proposed model for the putative additive NR1D1-GSK3β genetic contribution to Li response. A) Variant rs2071427 is associated with altered NR1D1 transcript ratios in the presence of Li. This may lead to an increase in the truncated Rev-Erbα protein isoform which is more stable, but unable to serve as a substrate for GSK3β phosphorylation. B) Variant rs6438552 is associated with lower GSK3β gene expression, which may subsequently reduce GSK3β protein levels. C) These mechanistically independent processes could additively oppose Rev-Erbα phosphorylation, altering protein stability and/or limiting Rev-Erbα’s role in processes requiring this modification.