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Background Gut microbiota is closely associated with host health and disease occurrence. Host genetic factor plays an important role in shaping gut microbial communities. The specific mechanism of host-regulated gene expression affecting gut microbiota has not been elucidated yet. Here we conducted a transcriptome-wide association study (TWAS) for gut microbiota by leveraging expression imputation from large-scale GWAS data sets. Results TWAS detected multiple tissue-specific candidate genes for gut microbiota, such as FUT2 for genus  Bifidobacterium  in transverse colon ( P  PERM.ANL  = 1.68 × 10 –3 ) and SFTPD for an unclassified genus of  Proteobacteria  in transverse colon ( P  PERM.ANL  = 5.69 × 10 –3 ). Fine mapping replicated 3 candidate genes in TWAS, such as HELLS for  Streptococcus  (PIP = 0.685) in sigmoid colon, ANO7 for  Erysipelotrichaceae  (PIP = 0.449) in sigmoid colon. Functional analyses detected 94 significant GO terms and 11 pathways for various taxa in total, such as GO_NUCLEOSIDE_DIPHOSPHATASE_ACTIVITY for  Butyrivibrio  (FDR  P  = 1.30 × 10 –4 ), KEGG_RENIN_ANGIOTENSIN_SYSTEM for  Anaerostipes  (FDR  P  = 3.16 × 10 –2 ). Literature search results showed 12 genes prioritized by TWAS were associated with 12 diseases. For instance, SFTPD for an unclassified genus of  Proteobacteria  was related to atherosclerosis, and FUT2 for  Bifidobacterium  was associated with Crohn’s disease. Conclusions Our study results provided novel insights for understanding the genetic mechanism of gut microbiota, and attempted to provide clues for revealing the influence of genetic factors on gut microbiota for the occurrence and development of diseases.

Transcriptome-wide association study identified candidate genes associated with gut microbiota