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Background The associations between sugary beverages and genetic predisposition to depression risk remain unclear.Aims This study aimed to investigate the associations of sugar-sweetened beverages (SSBs), artificially sweetened beverages (ASBs) and natural juices (NJs) with depression and to assess whether these associations were modified by genetic predisposition.Methods We used data from the UK Biobank of 180 599 individuals aged 39–72 years who were depression-free at baseline. Dietary intake of SSBs, ASBs and NJs was accessed by a 24-hour dietary recall between 2009 and 2012. The Polygenic Risk Score for depression was estimated and categorised as low (lowest tertile), intermediate (tertile 2) and high (highest tertile). Cox proportional hazard and substitution models were conducted to evaluate hazard ratios (HRs) and 95% CIs.Results Over the 12-year follow-up, 4915 individuals developed depression. Higher consumption (>2 units/day) of SSBs (HR: 1.26, 95% CI 1.12 to 1.43) and ASBs (HR: 1.40, 95% CI 1.23 to 1.60) were both associated with an increased risk of depression. However, moderate consumption (>0–1 units/day) of NJs was associated with a lower risk of depression (HR: 0.89, 95% CI 0.83 to 0.95). Furthermore, genetic predisposition did not modify these associations (p interaction>0.05). In substitution models, the HRs for depression risk were 0.94 (95% CI 0.89 to 0.99) and 0.89 (95% CI 0.85 to 0.94), respectively, when 1 unit/day of SSBs or ASBs was replaced by an equivalent intake of NJs.Conclusions Higher consumption of SSBs and ASBs was associated with an increased risk of depression; in contrast, moderate consumption of NJs was inversely associated with a lower risk of depression. In theory, substituting SSBs and ASBs with NJs would suppose a reduction of depression risk.