Fig. 2. Top E2-DRGs implicate ER–Golgi function and Ca²⁺ homeostasis in PMDD.

a GeneMANIA visualization of select E2-DRGs. Key genes relating to ER–Golgi function and intracellular calcium homeostasis (NUCB1, DST, GCC2, GOLGB1) were selected from among the top 10 E2-DRGs and included as inputs for GeneMANIA network visualization (genemania.org, accessed January 2019). The resulting output revealed a structural network of Golgi–ER-associated genes, with physical interactions comprising 67.6% of the weighted network. b qRT-PCR validation of select E2-DRGs. NUCB1, DHCR7, PPP2R5D, and GOLGB1 were selected for qRT-PCR validation in an independent replication cohort of 13 cases and 13 controls. NUCB1 qRT-PCR results revealed a significant main effect of diagnosis (F(1,24)=4.61, p = 0.042) and interaction of diagnosis and hormone (F(1,24)=7.01, p = 0.014). In post-hoc testing, E2-treated PMDD samples had significantly reduced NUCB1 expression compared to control samples (p = 0.003). qRT-PCR results for DHCR7 did not reveal significant effects of diagnosis, hormone, or their interaction, but in multiple comparisons testing, DHCR7 expression was significantly reduced in E2-treated PMDD samples compared to E2-treated control samples (p = 0.040). No significant differences for PPP2R5D or GOLGB1 were found in qRT-PCR validation.