Utilizing similar machine learning approaches to analyze clock gene associations with anxiety in a large UK Biobank dataset, we report three main findings: (1) Clock genotype combinations including ZBTB20 variants exhibit combination-specific effects on anxiety, (2) Clock variant combinations associated with anxiety tend to display sex-specific effects, and (3) Circadian-related variants linked to anxiety risk have both direct (chronotype-independent) influences and indirect (chronotype-mediated) influences on anxiety symptoms. This evidence concerns the gene ZBTB20 and Anxiety.