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Previous studies have suggested that vitamin D (VD) was associated with psychiatric diseases, but efforts to elucidate the functional relevance of VD with depression and anxiety from genetic perspective have been limited. Based on the UK Biobank cohort, we first calculated polygenic risk score (PRS) for VD from genome-wide association study (GWAS) data of VD. Linear and logistic regression analysis were conducted to evaluate the associations of VD traits with depression and anxiety traits, respectively. Then, using individual genotype and phenotype data from the UK Biobank, genome-wide environment interaction studies (GWEIS) were performed to identify the potential effects of gene × VD interactions on the risks of depression and anxiety traits. In the UK Biobank cohort, we observed significant associations of blood VD level with depression and anxiety traits, as well as significant associations of VD PRS and depression and anxiety traits. GWEIS identified multiple candidate loci, such as rs114086183 ( p = 4.11 × 10 -8 , LRRTM4) for self-reported depression status and rs149760119 ( p = 3.88 × 10 -8 , GNB5) for self-reported anxiety status. Our study results suggested that VD was negatively associated with depression and anxiety. GWEIS identified multiple candidate genes interacting with VD, providing novel clues for understanding the biological mechanism potential associations between VD and psychiatric disorders.

Disrupted brain structures and several life environmental factors have been shown to influence depression and anxiety, but their interactions with anxiety and depression remain elusive. Genome‐wide association study datasets of 15 brain structure longitudinal changes (N = 15,640) were obtained from the published study. Genotype and phenotype‐related data of depression, anxiety, and life environmental factors (including smoking, alcohol drinking, coffee intake, maternal smoking, physical activity, vitamin D, insomnia, sleep duration, and family satisfaction) were collected from UK Biobank. We calculated the polygenic risk scores (PRS) of 15 brain structure changes and then conducted linear regression analyses to explore the interactions of brain structure changes and life environmental factors on depression and anxiety using 15 brain structure change‐related PRS, life environmental factors and interactions of them as instrumental variables, and depression score or anxiety score as outcomes. Sex stratification in all analyses was performed to reveal sex‐specific differences in the interactions. We found 14 shared interactions related to both depression and anxiety in total sample, such as alcohol drinking × cerebellum white matter 3 (WM; beta = −.003, p =.018 for depression; beta = −003, p =.008 for anxiety) and maternal smoking × nucleus accumbens 2 (beta =.088, p =.002 for depression; beta =.070, p =.008 for anxiety). We also observed sex‐specific differences in the interactions, for instance, alcohol drinking × cerebellum WM 3 was negatively associated with depression and anxiety in males (beta = −.004, p =.020 for depression; beta = −.005, p =.002 for anxiety). Our study results reveal the important interactions between brain structure changes and several life environmental factors on depression and anxiety, which may help to explore the pathogenesis of depression and anxiety. [ABSTRACT FROM AUTHOR]