Sex specific effect of gut microbiota on the risk of psychiatric disorders: A Mendelian randomisation study and PRS analysis using UK Biobank cohort

Abstract

Objective

The relationships between gut microbiota and brain-related diseases/traits remains not fully understood.

Method

A two-stage study was performed to investigate the relationships between gut microbiota and brain-related diseases/traits, and evaluate the potential sex specific effects of gut microbiota. In discovery stage, we systematically scanned the relationships between 515 brain-related diseases/traits and gut microbiota through two-sample Mendelian randomisation analysis. Using ∼500,000 individuals derived from the UK Biobank, polygenetic risk scoring (PRS) analysis was performed to validate the associations detected in discovery stage. To evaluate the potential sex-specific effect of gut microbiota on brain-related disorders, PRS analysis was conducted in female and male, respectively.

Results

After systematically scanning diseases or traits, 41 of the 515 brain-related diseases/traits were identified to be associated with gut microbiota, such as Neuroticism score (P_2-MR = 0.0018), worrier/anxious feelings (P_2-MR = 0.0013), Suffer from ‘nerves’ (P_2-MR = 0.0062) and Nervous feelings (P_2-MR = 0.0158). 5 of 41 brain-related diseases or traits were successfully validated in UK Biobank, such as Neuroticism score (P_UK = 0.0024, P_UK-female = 0.0063, P_UK-male = 0.1142), Nervous feelings (P_UK = 0.0043, P_UK-female = 0.0115, P_UK-male = 0.1670) and Worrier/anxious feelings (P_UK = 0.0166, P_UK-female = 0.0196, P_UK-male = 0.2930).

Conclusion

Our results suggest that gut microbiota contributed more to brain-related diseases or traits in females than in males.

Key points

• A two-stage study was performed to investigate the relationships between gut microbiota and brain-related diseases/traits.

• Using the individuals derived from the UK Biobank, polygenetic risk scoring analysis was performed to validate the associations detected in the discovery stage.

• Our results suggest that gut microbiota contributed more to brain-related diseases or traits in females than in males.

Keywords:

• Gut microbiota
• brain
• sex specific
• psychiatric disorders
• neurological disorders

Acknowledgements

We thank the UK Biobank participants and the UK Biobank team for their work in collecting, processing and disseminating these data for analysis. The UK Biobank study was approved by the National Health Service National Research Ethics Service (11/NW/0382). Our data dictionary ID for application is 46478.

Statement of interest

The authors have stated that they have no conflict of interest.

Author contributions

Xin Qi and Fanglin Guan drafted the manuscript. Feng Zhang designed the study. Xin Qi, Zhang, Fanglin Guan, Shiqiang Cheng, Yan Wen and Li Liu performed the statistical analyses. Mei Ma, Bolun Cheng, Chujun Liang, Xiao Liang, Lu Zhang, Ping Li, Xiaomeng Chu, Jing Ye, and Yao Yao provided feasible advice on data analysis and drafting manuscript. All authors read and approved the final manuscript. All authors discussed the results and commented on the manuscript.

Data availability statement

Data sharing is not applicable to this article as no datasets were generated or analysed during the current study.

Additional information

Funding

This study is supported by the National Natural Scientific Foundation of China [81472925, 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.