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Background: Brain‑derived neurotrophic factor (BDNF), the most abundant and widely expressed neurotrophin in the brain, is believed to play an important role in depression and anxiety. In this study, we hypothesized that single‑nucleotide polymorphisms (SNPs) within the BDNF gene should be linked with depression and anxiety through complex interactions in the general population. Methods: We analyzed 7,098 Taiwanese participants from the Taiwan Biobank. Measures of anxiety and depression were evaluated using the Patient Health Questionnaire‑4 (PHQ‑4). We used 43 BDNF polymorphisms in the genetic analysis. Results: We found a nominal association between nine BDNF genetic variants and depression state, after having adjusted for the factors of age and gender. Furthermore, three BDNF SNPs showed evidence of nominal association with PHQ‑4 scores. In addition, an interaction significantly existed between the BDNF rs73430670 and BDNF rs4923461 in influencing depression state (p < 0.05). Finally, we found that influence of interaction significantly existed between BDNF rs12418745 and physical activity (p < 0.05) in depression state. Conclusion: Those results suggest that the BDNF genetic variants may contribute to psychological distress independently as well as through SNP‑SNP and gene‑physical activity interactions in the general population.