Psychiatric disorders are a group of complex psychological syndromes with high prevalence. It has been reported that gut microbiota has a dominant influence on the risks of psychiatric disorders through gut microbiota–brain axis. We extended the classic gene set enrichment analysis (GSEA) approach to detect the association between gut microbiota and complex diseases using published genome-wide association study (GWAS) and GWAS of gut microbiota summary data. We applied our approach to real GWAS data sets of five psychiatric disorders, including attention deficiency/hyperactive disorder (ADHD), autism spectrum disorder (AUT), bipolar disorder (BD), schizophrenia (SCZ) and major depressive disorder (MDD). To evaluate the performance of our approach, we also tested the genetic correlations of obesity and type 2 diabetes with gut microbiota. We identified several significant associations between psychiatric disorders and gut microbiota, such as ADHD and genus Desulfovibrio (P = 0.031), order Clostridiales (P = 0.034). For AUT, association signals were observed for genera Bacteroides (P = 0.012) and Desulfovibrio (P = 0.033). Genus Desulfovibrio (P = 0.005) appeared to be associated with BD. For MDD, association signals were observed for genus Desulfovibrio (P = 0.003), order Clostridiales (P = 0.004), family Lachnospiraceae (P = 0.007) and genus Bacteroides (P = 0.007). Genus Desulfovibrio (P = 0.012) and genus Bacteroides (P = 0.038) appeared to be associated with SCZ. Our study results provide novel clues for revealing the roles of gut microbiota in psychiatric disorders. This study also illustrated the good performance of GSEA approach for exploring the relationships between gut microbiota and complex diseases.

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Background: Recent study demonstrates the comprehensive effects of gut microbiota on complex diseases or traits. However, limited effort has been conducted to explore the potential relationships between gut microbiota and BMD. Methods:We performed a polygenetic risk scoring (PRS) analysis to systematically explore the relationships between gut microbiota and body BMD. Significant SNP sets associated with gut microbiota were derived from previous genome-wide association study (GWAS). In total, 2,294 to 5,065 individuals with BMD values of different sites and their genotype data were obtained from UK Biobank cohort. The gut microbiota PRS of each individual was computed from the SNP genotype data for each study subject of UK Biobank by PLINK software. Using computed PRS as the instrumental variables of gut microbiota, Pearson correlation analysis of individual PRS values and BMD values was finally conducted to test the potential association between gut microbiota and target trait.Results: In total, 31 BMD traits were selected as outcome to assess their relationships with gut microbiota. After adjusted for age, sex, body mass index, and the first 5 principal components (PCs) as the covariates using linear regression model, pelvis BMD (P = 0.0437) showed suggestive association signal with gut microbiota after multiple testing correction. Conclusion:Our study findings support the weak relevance of gut microbiota with the development of BMD.