Network-based quantitative trait linkage analysis of microbiome composition in inflammatory bowel disease families
Introduction: Inflammatory bowel disease (IBD) is characterized by a dysbiosis of the gut microbiome that results from the interaction of the constituting taxa with one another, and with the host. At the same time, host genetic variation is associated with both IBD risk and microbiome composition.Me...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2023.1048312/full |
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| author | Arunabh Sharma Olaf Junge Silke Szymczak Malte Christoph Rühlemann Malte Christoph Rühlemann Janna Enderle Stefan Schreiber Stefan Schreiber Matthias Laudes Andre Franke Wolfgang Lieb Michael Krawczak Astrid Dempfle |
| author_facet | Arunabh Sharma Olaf Junge Silke Szymczak Malte Christoph Rühlemann Malte Christoph Rühlemann Janna Enderle Stefan Schreiber Stefan Schreiber Matthias Laudes Andre Franke Wolfgang Lieb Michael Krawczak Astrid Dempfle |
| author_sort | Arunabh Sharma |
| collection | DOAJ |
| description | Introduction: Inflammatory bowel disease (IBD) is characterized by a dysbiosis of the gut microbiome that results from the interaction of the constituting taxa with one another, and with the host. At the same time, host genetic variation is associated with both IBD risk and microbiome composition.Methods: In the present study, we defined quantitative traits (QTs) from modules identified in microbial co-occurrence networks to measure the inter-individual consistency of microbial abundance and subjected these QTs to a genome-wide quantitative trait locus (QTL) linkage analysis.Results: Four microbial network modules were consistently identified in two cohorts of healthy individuals, but three of the corresponding QTs differed significantly between IBD patients and unaffected individuals. The QTL linkage analysis was performed in a sub-sample of the Kiel IBD family cohort (IBD-KC), an ongoing study of 256 German families comprising 455 IBD patients and 575 first- and second-degree, non-affected relatives. The analysis revealed five chromosomal regions linked to one of three microbial module QTs, namely on chromosomes 3 (spanning 10.79 cM) and 11 (6.69 cM) for the first module, chr9 (0.13 cM) and chr16 (1.20 cM) for the second module, and chr13 (19.98 cM) for the third module. None of these loci have been implicated in a microbial phenotype before.Discussion: Our study illustrates the benefit of combining network and family-based linkage analysis to identify novel genetic drivers of microbiome composition in a specific disease context. |
| first_indexed | 2024-04-10T20:50:25Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-10T20:50:25Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-91fa72aa6b65437387731be53cf7f4692023-01-23T13:37:03ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-01-011410.3389/fgene.2023.10483121048312Network-based quantitative trait linkage analysis of microbiome composition in inflammatory bowel disease familiesArunabh Sharma0Olaf Junge1Silke Szymczak2Malte Christoph Rühlemann3Malte Christoph Rühlemann4Janna Enderle5Stefan Schreiber6Stefan Schreiber7Matthias Laudes8Andre Franke9Wolfgang Lieb10Michael Krawczak11Astrid Dempfle12Institute of Medical Informatics and Statistics, Kiel University, Kiel, GermanyInstitute of Medical Informatics and Statistics, Kiel University, Kiel, GermanyInstitute of Medical Biometry and Statistics, University of Lübeck, Lübeck, GermanyInstitute of Clinical Molecular Biology, Kiel University, Kiel, GermanyInstitute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, GermanyInstitute of Epidemiology, Kiel University, Kiel, GermanyInstitute of Clinical Molecular Biology, Kiel University, Kiel, GermanyDepartment of Internal Medicine I, University Hospital Schleswig-Holstein, Kiel, GermanyInstitute of Diabetology and Clinical Metabolic Research, Kiel University, Kiel, GermanyInstitute of Clinical Molecular Biology, Kiel University, Kiel, GermanyInstitute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, GermanyInstitute of Medical Informatics and Statistics, Kiel University, Kiel, GermanyInstitute of Medical Informatics and Statistics, Kiel University, Kiel, GermanyIntroduction: Inflammatory bowel disease (IBD) is characterized by a dysbiosis of the gut microbiome that results from the interaction of the constituting taxa with one another, and with the host. At the same time, host genetic variation is associated with both IBD risk and microbiome composition.Methods: In the present study, we defined quantitative traits (QTs) from modules identified in microbial co-occurrence networks to measure the inter-individual consistency of microbial abundance and subjected these QTs to a genome-wide quantitative trait locus (QTL) linkage analysis.Results: Four microbial network modules were consistently identified in two cohorts of healthy individuals, but three of the corresponding QTs differed significantly between IBD patients and unaffected individuals. The QTL linkage analysis was performed in a sub-sample of the Kiel IBD family cohort (IBD-KC), an ongoing study of 256 German families comprising 455 IBD patients and 575 first- and second-degree, non-affected relatives. The analysis revealed five chromosomal regions linked to one of three microbial module QTs, namely on chromosomes 3 (spanning 10.79 cM) and 11 (6.69 cM) for the first module, chr9 (0.13 cM) and chr16 (1.20 cM) for the second module, and chr13 (19.98 cM) for the third module. None of these loci have been implicated in a microbial phenotype before.Discussion: Our study illustrates the benefit of combining network and family-based linkage analysis to identify novel genetic drivers of microbiome composition in a specific disease context.https://www.frontiersin.org/articles/10.3389/fgene.2023.1048312/fulllinkage analysisgut microbiomeinflammatory bowel diseasefamily-based study designmicrobiome co-occurrence network |
| spellingShingle | Arunabh Sharma Olaf Junge Silke Szymczak Malte Christoph Rühlemann Malte Christoph Rühlemann Janna Enderle Stefan Schreiber Stefan Schreiber Matthias Laudes Andre Franke Wolfgang Lieb Michael Krawczak Astrid Dempfle Network-based quantitative trait linkage analysis of microbiome composition in inflammatory bowel disease families Frontiers in Genetics linkage analysis gut microbiome inflammatory bowel disease family-based study design microbiome co-occurrence network |
| title | Network-based quantitative trait linkage analysis of microbiome composition in inflammatory bowel disease families |
| title_full | Network-based quantitative trait linkage analysis of microbiome composition in inflammatory bowel disease families |
| title_fullStr | Network-based quantitative trait linkage analysis of microbiome composition in inflammatory bowel disease families |
| title_full_unstemmed | Network-based quantitative trait linkage analysis of microbiome composition in inflammatory bowel disease families |
| title_short | Network-based quantitative trait linkage analysis of microbiome composition in inflammatory bowel disease families |
| title_sort | network based quantitative trait linkage analysis of microbiome composition in inflammatory bowel disease families |
| topic | linkage analysis gut microbiome inflammatory bowel disease family-based study design microbiome co-occurrence network |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2023.1048312/full |
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