G.C.TAN1, Y.X. LOO2, A. TAN2, Y.X.S. TEY1, M. KEE3, H. ZHOU2, Z.M. NGOH3, S. YEO3, T. SUPRAPMO2, J. LIM2, M.J. MEANEY3
Institute of Mental Health1, National University of Singapore2, Agency for Science, Technology and Research (A*STAR)3
Genetic risk for depression has been causally related to the risk for coronary artery disease, which is partially mediated by effects on lipids and lipids have been shown to be a chronic marker of stress. Here we sought to test the hypothesis that candidate genes influencing lipid levels influence childhood depression and to identify brain correlates.
A TWAS of LDL-C was conducted using GWAS summary statistics obtained from a meta-analysis of LDL in 173082 Europeans and 32285 East Asians. TWAS-significant genes were input into Reactome to identify those involved in neuronal signalling. Regional brain expression of the genes were estimated in 368 Singaporean children from the GUSTO study with PrediXcan. Linear regression models adjusted for sex and population stratification were fitted to predict CDI2 (Children’s Depression Inventory 2), and subsequently on the volume of brain regions associated with depression.
5 TWAS-significant genes (HOMER3, ALDH2, SLC22A1, KCNN4, SYT7) were involved in neuronal signalling. Children with higher Synaptotagmin-7 (SYT7) expression in the cerebellum have higher CDI2 scores (β = 4.5466, p = 0.00194) while the other 4 genes were not associated. Children with higher SYT7 expression had larger volumes of right medial orbitofrontal cortex (β = 413.85, p=0.019), and right isthmus of cingulate gyrus (β = 208.881, p=0.0375).
SYT7 brain expression is associated with severity of depressive symptoms and orbitofrontal and cingulate cortex volume in a community sample of children. SYT7 is implicated in cholesterol transport, synaptic transmission and bipolar disorder and shows potential as a marker for personalized medicine.