Genetic effects on the commensal microbiota in inflammatory bowel disease patients.
Several bacteria in the gut microbiota have been shown to be associated with inflammatory bowel disease (IBD), and dozens of IBD genetic variants have been identified in genome-wide association studies. However, the role of the microbiota in the etiology of IBD in terms of host genetic susceptibilit...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2019-03-01
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| Series: | PLoS Genetics |
| Online Access: | https://doi.org/10.1371/journal.pgen.1008018 |
| _version_ | 1819133076492517376 |
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| author | Hugues Aschard Vincent Laville Eric Tchetgen Tchetgen Dan Knights Floris Imhann Philippe Seksik Noah Zaitlen Mark S Silverberg Jacques Cosnes Rinse K Weersma Ramnik Xavier Laurent Beaugerie David Skurnik Harry Sokol |
| author_facet | Hugues Aschard Vincent Laville Eric Tchetgen Tchetgen Dan Knights Floris Imhann Philippe Seksik Noah Zaitlen Mark S Silverberg Jacques Cosnes Rinse K Weersma Ramnik Xavier Laurent Beaugerie David Skurnik Harry Sokol |
| author_sort | Hugues Aschard |
| collection | DOAJ |
| description | Several bacteria in the gut microbiota have been shown to be associated with inflammatory bowel disease (IBD), and dozens of IBD genetic variants have been identified in genome-wide association studies. However, the role of the microbiota in the etiology of IBD in terms of host genetic susceptibility remains unclear. Here, we studied the association between four major genetic variants associated with an increased risk of IBD and bacterial taxa in up to 633 IBD cases. We performed systematic screening for associations, identifying and replicating associations between NOD2 variants and two taxa: the Roseburia genus and the Faecalibacterium prausnitzii species. By exploring the overall association patterns between genes and bacteria, we found that IBD risk alleles were significantly enriched for associations concordant with bacteria-IBD associations. To understand the significance of this pattern in terms of the study design and known effects from the literature, we used counterfactual principles to assess the fitness of a few parsimonious gene-bacteria-IBD causal models. Our analyses showed evidence that the disease risk of these genetic variants were likely to be partially mediated by the microbiome. We confirmed these results in extensive simulation studies and sensitivity analyses using the association between NOD2 and F. prausnitzii as a case study. |
| first_indexed | 2024-12-22T09:41:33Z |
| format | Article |
| id | doaj.art-8c349ae121624087adba7f192a9d3f0c |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-22T09:41:33Z |
| publishDate | 2019-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-8c349ae121624087adba7f192a9d3f0c2022-12-21T18:30:39ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042019-03-01153e100801810.1371/journal.pgen.1008018Genetic effects on the commensal microbiota in inflammatory bowel disease patients.Hugues AschardVincent LavilleEric Tchetgen TchetgenDan KnightsFloris ImhannPhilippe SeksikNoah ZaitlenMark S SilverbergJacques CosnesRinse K WeersmaRamnik XavierLaurent BeaugerieDavid SkurnikHarry SokolSeveral bacteria in the gut microbiota have been shown to be associated with inflammatory bowel disease (IBD), and dozens of IBD genetic variants have been identified in genome-wide association studies. However, the role of the microbiota in the etiology of IBD in terms of host genetic susceptibility remains unclear. Here, we studied the association between four major genetic variants associated with an increased risk of IBD and bacterial taxa in up to 633 IBD cases. We performed systematic screening for associations, identifying and replicating associations between NOD2 variants and two taxa: the Roseburia genus and the Faecalibacterium prausnitzii species. By exploring the overall association patterns between genes and bacteria, we found that IBD risk alleles were significantly enriched for associations concordant with bacteria-IBD associations. To understand the significance of this pattern in terms of the study design and known effects from the literature, we used counterfactual principles to assess the fitness of a few parsimonious gene-bacteria-IBD causal models. Our analyses showed evidence that the disease risk of these genetic variants were likely to be partially mediated by the microbiome. We confirmed these results in extensive simulation studies and sensitivity analyses using the association between NOD2 and F. prausnitzii as a case study.https://doi.org/10.1371/journal.pgen.1008018 |
| spellingShingle | Hugues Aschard Vincent Laville Eric Tchetgen Tchetgen Dan Knights Floris Imhann Philippe Seksik Noah Zaitlen Mark S Silverberg Jacques Cosnes Rinse K Weersma Ramnik Xavier Laurent Beaugerie David Skurnik Harry Sokol Genetic effects on the commensal microbiota in inflammatory bowel disease patients. PLoS Genetics |
| title | Genetic effects on the commensal microbiota in inflammatory bowel disease patients. |
| title_full | Genetic effects on the commensal microbiota in inflammatory bowel disease patients. |
| title_fullStr | Genetic effects on the commensal microbiota in inflammatory bowel disease patients. |
| title_full_unstemmed | Genetic effects on the commensal microbiota in inflammatory bowel disease patients. |
| title_short | Genetic effects on the commensal microbiota in inflammatory bowel disease patients. |
| title_sort | genetic effects on the commensal microbiota in inflammatory bowel disease patients |
| url | https://doi.org/10.1371/journal.pgen.1008018 |
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