CLOCK and major depressive disorder: More importantly, in spite of a lack of a main effect of CLOCK variation on depressive phenotypes, we did detect a robust effect of several clumps of SNPs on current depressive symptoms in interaction with both distal, early childhood, and proximal, recent stressors, which is in line with our paradigm postulating that the majority of genes impact depression by increasing susceptibility toward the negative effects of stress rather than exerting a direct effect (16, 21).