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Microbiota Analysis Using Two-step PCR and Next-generation 16S rRNA Gene Sequencing
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Transcriptome-wide association study identified candidate genes associated with gut microbiota.

Chuyu Pan1, Yujie Ning1, Yumeng Jia1

  • 1Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, National Health Commission of the People's Republic of China, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, 71006, China.

Gut Pathogens
|December 19, 2021
PubMed
Summary

This study used transcriptome-wide association studies (TWAS) to identify host genes influencing gut microbiota composition. Findings link specific genes to bacterial taxa and associated diseases, offering insights into host genetic regulation of the gut microbiome.

Keywords:
Genome-wide association study (GWAS)Gut microbiotaPathwayTranscriptome-wide association study (TWAS)

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Area of Science:

  • Genetics
  • Microbiology
  • Systems Biology

Background:

  • Gut microbiota composition is crucial for host health and disease.
  • Host genetics significantly influence gut microbial communities.
  • The precise mechanisms of host gene regulation on gut microbiota remain unclear.

Purpose of the Study:

  • To investigate the genetic underpinnings of gut microbiota composition using transcriptome-wide association studies (TWAS).
  • To identify host genes that regulate specific gut microbial taxa.
  • To explore the association between host genetic factors, gut microbiota, and disease development.

Main Methods:

  • Performed a transcriptome-wide association study (TWAS) by leveraging expression imputation from large-scale genome-wide association study (GWAS) data.
  • Utilized fine mapping to replicate candidate genes.
  • Conducted functional analyses, including Gene Ontology (GO) and pathway enrichment analyses.
  • Cross-referenced identified genes with disease associations through literature search.

Main Results:

  • TWAS identified multiple tissue-specific candidate genes associated with gut microbiota, including FUT2 for Bifidobacterium and SFTPD for Proteobacteria in the transverse colon.
  • Fine mapping replicated candidate genes like HELLS for Streptococcus and ANO7 for Erysipelotrichaceae in the sigmoid colon.
  • Functional analyses revealed significant GO terms and pathways, such as NUCLEOSIDE DIPHOSPHATASE ACTIVITY and the RENIN ANGIOTENSIN SYSTEM.
  • Twelve prioritized genes were associated with 12 different diseases, with SFTPD linked to atherosclerosis and FUT2 to Crohn's disease.

Conclusions:

  • The study provides novel insights into the genetic mechanisms governing gut microbiota composition.
  • Identified host genes and their associated microbial taxa offer potential targets for understanding disease etiology.
  • Results suggest a significant role for host genetic factors in modulating gut microbiota and influencing disease development.