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Whole exome sequencing analyses reveal gene-microbiota interactions in the context of IBD
- Source :
- Gut, 70(2):319706, 285-296. BMJ PUBLISHING GROUP, Gut
- Publication Year :
- 2021
-
Abstract
- ObjectiveBoth the gut microbiome and host genetics are known to play significant roles in the pathogenesis of IBD. However, the interaction between these two factors and its implications in the aetiology of IBD remain underexplored. Here, we report on the influence of host genetics on the gut microbiome in IBD.DesignTo evaluate the impact of host genetics on the gut microbiota of patients with IBD, we combined whole exome sequencing of the host genome and whole genome shotgun sequencing of 1464 faecal samples from 525 patients with IBD and 939 population-based controls. We followed a four-step analysis: (1) exome-wide microbial quantitative trait loci (mbQTL) analyses, (2) a targeted approach focusing on IBD-associated genomic regions and protein truncating variants (PTVs, minor allele frequency (MAF) >5%), (3) gene-based burden tests on PTVs with MAF ResultsWe identified 12 mbQTLs, including variants in the IBD-associated genes IL17REL, MYRF, SEC16A and WDR78. For example, the decrease of the pathway acetyl-coenzyme A biosynthesis, which is involved in short chain fatty acids production, was associated with variants in the gene MYRF (false discovery rate CYP2D6, GPR151 and CD160 genes. These genes are known for their function in the immune system. Moreover, interaction analyses confirmed previously known IBD disease-specific mbQTLs in TNFSF15.ConclusionThis study highlights that both common and rare genetic variants affecting the immune system are key factors in shaping the gut microbiota in the context of IBD and pinpoints towards potential mechanisms for disease treatment.
- Subjects :
- Adult
Male
DNA Copy Number Variations
SUSCEPTIBILITY LOCI
Quantitative Trait Loci
Population
Vesicular Transport Proteins
intestinal microbiology
Context (language use)
Genome-wide association study
DETERMINANTS
Biology
Gut flora
VARIANTS
digestive system
GUT MICROBIOME
HOST GENETICS
ACTIVATION
PROTEIN-COUPLED RECEPTORS
Gene Frequency
Exome Sequencing
Humans
genetics
Genetic Predisposition to Disease
GENOME-WIDE ASSOCIATION
education
Gene
Exome sequencing
Adaptor Proteins, Signal Transducing
Genetics
education.field_of_study
Receptors, Interleukin-17
Shotgun sequencing
Inflammatory Bowel Disease
Gastroenterology
Membrane Proteins
Middle Aged
Inflammatory Bowel Diseases
biology.organism_classification
FRAMEWORK
Gastrointestinal Microbiome
Minor allele frequency
Case-Control Studies
Female
Metagenomics
Transcription Factors
INFLAMMATORY-BOWEL-DISEASE
Subjects
Details
- Language :
- English
- ISSN :
- 00175749
- Volume :
- 70
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Gut
- Accession number :
- edsair.doi.dedup.....21eb9555deaaa02faf9299a8e3ed84ed