Whole exome sequencing analyses reveal gene-microbiota interactions in the context of IBD.
Adaptor Proteins, Signal Transducing
/ genetics
Adult
Case-Control Studies
DNA Copy Number Variations
/ genetics
Female
Gastrointestinal Microbiome
/ genetics
Gene Frequency
/ genetics
Genetic Predisposition to Disease
/ genetics
Humans
Inflammatory Bowel Diseases
/ etiology
Male
Membrane Proteins
/ genetics
Metagenomics
Middle Aged
Quantitative Trait Loci
/ genetics
Receptors, Interleukin-17
/ genetics
Transcription Factors
/ genetics
Vesicular Transport Proteins
/ genetics
Exome Sequencing
genetics
inflammatory bowel disease
intestinal microbiology
Journal
Gut
ISSN: 1468-3288
Titre abrégé: Gut
Pays: England
ID NLM: 2985108R
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
23
08
2019
revised:
08
04
2020
accepted:
20
04
2020
pubmed:
12
7
2020
medline:
8
9
2021
entrez:
12
7
2020
Statut:
ppublish
Résumé
Both 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. To 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 <5% and exome copy number variations (CNVs) with site frequency <1%, (4) joint analysis of both cohorts to identify the interactions between disease and host genetics. We identified 12 mbQTLs, including variants in the IBD-associated genes This 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.
Identifiants
pubmed: 32651235
pii: gutjnl-2019-319706
doi: 10.1136/gutjnl-2019-319706
pmc: PMC7815889
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
CABIN1 protein, human
0
IL17REL protein, human
0
Membrane Proteins
0
Myrf protein, human
0
Receptors, Interleukin-17
0
SEC16A protein, human
0
Transcription Factors
0
Vesicular Transport Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
285-296Subventions
Organisme : NHGRI NIH HHS
ID : R01 HG010140
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH115957
Pays : United States
Organisme : NIMH NIH HHS
ID : R56 MH115957
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG009080
Pays : United States
Informations de copyright
© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: None declared.
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