We report three findings: (1) synergistic interactions between variants in PER3B, CLOCK3111, and cryptochrome genes, CRY1 and CRY2, show robust associations with anxiety symptoms, (2) clock variants predictive of anxiety symptoms tend to have sex-specific effects, and (3) molecular chronotype (circadian phase) and circadian misalignment—particularly individuals with advanced phases and evening-type sleep–wake cycles—are strong predictors of anxiety symptoms. This evidence concerns the gene CLOCK and Anxiety.