Abstract
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.