SLC6A4 and depressive symptom measurement: As demonstrated in Section 3, IG-GSCA was able to specify complex directional relationships among genes, ROIs, and depression severity in a more biologically plausible way based on previous knowledge, and to identify the influences of a gene (DRD2) and a gene-environment interaction (PTE x SLC6A4) on several brain regions, which in turn affected depression severity.