Figure 1. BHLHE41 is a strong contributor to the association between lithium response and the core clock geneset.

(A) MAGMA analyses based on circadian gene-sets in psychiatric traits. Competitive test P-values in the X-axis are −log10 converted. Dashed blue line indicates the Bonferroni significance threshold (P<0.05/8 gene-sets × 9 traits). Dashed red line indicates the nominal (uncorrected) significance threshold P=0.05. (B) In gene-based tests three genes reach nominal significance (unadjusted p-value). (C-E) Local Manhattan plots of these genes (+/− 15 KB) for dichotomous lithium response show the BHLHE41 locus (C) has the strongest association (5 SNPs with r² > 0.8) compared to CSNK1E (D) and RORB (E). ADHD: Attention- Deficit/Hyperactivity Disorder; PTSD: Post-Traumatic Stress Disorder.