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Background  Genetic factors may interplay with environmental stressors to contribute to risks of depressive symptoms. This study aimed to investigate the association of  FKBP5  polymorphisms and DNA methylation with depressive symptoms among Chinese adolescents, considering the role of parenting style.    Methods  This study used a nested case-control study design based on a cohort study, and the case ( n  = 120) and control groups ( n  = 118) were matched with age. Depressive symptoms, parenting style, and other demographics were measured. Fourteen potential polymorphisms and one promoter region in the  FKBP5  gene were selected for genotyping and methylation analysis.    Results  In the adjusted models, a significant association between  FKBP5  rs7757037 and depressive symptoms was found in the codominant model (AG vs. GG; adjusted odds ratio [AOR] = 2.56, 95% CI = 1.13–5.78) and dominant model (AA+AG vs. GG; AOR = 2.38, 95% CI = 1.11–5.120); rs2817032 and rs2817035 polymorphisms were associated with depressive symptoms in the codominant model and dominant model. Significant interactions between rs7757037 and the father’s parenting style were found in the codominant model ( P  = 0.043) and dominant model ( P  = 0.043), but the gene-environment interactions were not significant after correcting for multiple testing. Moreover, the significant main effects of  FKBP5  methylation status on depressive symptoms were not observed, and there was no significant interaction between  FKBP5  methylation status and parenting style on depressive symptoms.    Conclusions  Further studies are required to confirm the effect of  FKBP5  polymorphisms and methylation as well as their interactions with parenting styles in larger samples.    Supplementary Information  The online version contains supplementary material available at 10.1186/s12888-021-03576-6.

Associations of FKBP5 polymorphisms and methylation and parenting style with depressive symptoms among Chinese adolescents