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

Xin Qi; Fanglin Guan; Shiqiang Cheng; Yan Wen; Li Liu; Mei Ma; Bolun Cheng; Chujun Liang; Lu Zhang; Xiao Liang; Ping Li; Xiaomeng Chu; Jing Ye; Yao Yao; Feng Zhang

doi:10.1080/15622975.2021.1878428

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

World J Biol Psychiatry. 2021 Sep;22(7):495-504. doi: 10.1080/15622975.2021.1878428. Epub 2021 Apr 9.

Authors

Xin Qi^{1

2}, Fanglin Guan³, Shiqiang Cheng¹, Yan Wen¹, Li Liu¹, Mei Ma¹, Bolun Cheng¹, Chujun Liang¹, Lu Zhang¹, Xiao Liang⁴, Ping Li¹, Xiaomeng Chu¹, Jing Ye¹, Yao Yao¹, Feng Zhang¹

Affiliations

¹ Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, P. R. China.
² Precision Medicine Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, P. R. China.
³ School of Medicine and Forensics, Xi'an Jiaotong University, Xi'an, P. R. China.
⁴ The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, P. R. China.

PMID: 33834943
DOI: 10.1080/15622975.2021.1878428

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 pointsA 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; neurological disorders; psychiatric disorders; sex specific.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biological Specimen Banks
Female
Gastrointestinal Microbiome*
Genome-Wide Association Study
Humans
Male
Mental Disorders*
United Kingdom

Abstract

Publication types

MeSH terms

Grants and funding