Abstract
We aim to explore the potential interaction effects of brain aging and gut microbiota on the risks of sleep, anxiety and depression disorders. The genome-wide association study (GWAS) datasets of brain aging (N = 21,407) and gut microbiota (N = 3,890) were obtained from published studies. Individual level genotype and phenotype data of psychiatric traits (including sleep, anxiety and depression) were all from the UK Biobank (N = 107,947–374,505). We first calculated the polygenic risk scores (PRS) of 62 brain aging modes and 114 gut microbiota taxa as the instrumental variables, and then constructed linear and logistic regression analyses to systematically explore the potential interaction effects of brain aging and gut microbiota on psychiatric disorders. We observed the interaction effects of brain aging and gut microbiota on sleep, anxiety and depression disorders, such as Putamen/caudate T2* vs. Rhodospirillales (β = -0.012, P = 8.4 × 10–4) was negatively associated with chronotype, Fornix MD vs. Holdemanella (β = -0.007, P = 1.76 × 10–2) was negatively related to general anxiety disorder (GAD) scores, and White matter lesions vs. Acidaminococcaceae (β = 0.019, P = 1.29 × 10–3) was positively correlated with self-reported depression. Interestingly, Putamen volume vs. Intestinibacter was associated with all three psychiatric disorders, including chronotype (negative correlation), GAD scores (positive correlation) and self-reported depression (positive correlation). Our study results suggest the significant impacts of brain aging and gut microbiota on the development of sleep, anxiety and depression disorders, providing new clues for clarifying the pathogenesis of these disorders.
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Data availability
The UKB data are available through the UK Biobank Access Management System (https://www.ukbiobank.ac.uk/). We will return the derived data fields following UKB policy; in due course, they will be available through the UK Biobank Access Management System.
Code availability
Not applicable.
References
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Acknowledgements
This research was conducted under the UK Biobank application 46478.
Funding
This study is supported by the National Natural Scientific Foundation of China (81673112, 81703177); the Key projects of international cooperation among governments in scientific and technological innovation (2016YFE0119100); the Natural Science Basic Research Plan in Shaanxi Province of China (2017JZ024); and the Fundamental Research Funds for the Central Universities (xzy022019006). National Natural Science Foundation of China,81673112,Feng Zhang,81703177,Feng Zhang,Key projects of international cooperation among governments in scientific and technological innovation,2016YFE0119100,Feng Zhang,Natural Science Foundation of Shaanxi Province,2017JZ024,Feng Zhang,Fundamental Research Funds for the Central Universities,xzy022019006,Feng Zhang
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Author contributions included conception and study design (H.Z. and F.Z.), data collection or acquisition (X.Y., P.M., C.L., C.P., Y.C., J.Z., Z.Z., Y.W. and Y.J), statistical analysis (S.C.), interpretation of results (H.Z. and L.L), drafting the manuscript work or revising it critically for important intellectual content (H.Z. and L.L) and approval of final version to be published and agreement to be accountable for the integrity and accuracy of all aspects of the work (All authors).
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UK Biobank has approval from the North West Multi-centre Research Ethics Committee (MREC) and Human Tissue Authority (HTA). This study was conducted with the permission (UKB application 46,478) from the UK Biobank.
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Zhang, H., Liu, L., Cheng, S. et al. Assessing the joint effects of brain aging and gut microbiota on the risks of psychiatric disorders. Brain Imaging and Behavior 16, 1504–1515 (2022). https://doi.org/10.1007/s11682-022-00630-z
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DOI: https://doi.org/10.1007/s11682-022-00630-z