CLOCK and major depressive disorder: However, the most recent and very large, hypothesis-free genome-wide association studies of major depressive disorder (MD)—a 2025 trans-ancestry meta-analysis of 688,808 cases and 4,364,225 controls—have identified 697 independent SNP associations at 635 loci but did not prioritize canonical clock genes among the 308 high-confidence genes associated with MD; instead, the hits were enriched for synaptic and neuronal signaling genes [64].