Cargando…

Linkage analysis identifies novel genetic modifiers of microbiome traits in families with inflammatory bowel disease

Dysbiosis of the gut microbiome is a hallmark of inflammatory bowel disease (IBD) and both, IBD risk and microbiome composition, have been found to be associated with genetic variation. Using data from families of IBD patients, we examined the association between genetic and microbiome similarity in...

Descripción completa

Detalles Bibliográficos
Autores principales: Sharma, Arunabh, Szymczak, Silke, Rühlemann, Malte, Freitag-Wolf, Sandra, Knecht, Carolin, Enderle, Janna, Schreiber, Stefan, Franke, Andre, Lieb, Wolfgang, Krawczak, Michael, Dempfle, Astrid
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8820822/
https://www.ncbi.nlm.nih.gov/pubmed/35129060
http://dx.doi.org/10.1080/19490976.2021.2024415
_version_ 1784646287981805568
author Sharma, Arunabh
Szymczak, Silke
Rühlemann, Malte
Freitag-Wolf, Sandra
Knecht, Carolin
Enderle, Janna
Schreiber, Stefan
Franke, Andre
Lieb, Wolfgang
Krawczak, Michael
Dempfle, Astrid
author_facet Sharma, Arunabh
Szymczak, Silke
Rühlemann, Malte
Freitag-Wolf, Sandra
Knecht, Carolin
Enderle, Janna
Schreiber, Stefan
Franke, Andre
Lieb, Wolfgang
Krawczak, Michael
Dempfle, Astrid
author_sort Sharma, Arunabh
collection PubMed
description Dysbiosis of the gut microbiome is a hallmark of inflammatory bowel disease (IBD) and both, IBD risk and microbiome composition, have been found to be associated with genetic variation. Using data from families of IBD patients, we examined the association between genetic and microbiome similarity in a specific IBD context, followed by a genome-wide quantitative trait locus (QTL) linkage analysis of various microbiome traits using the same data. SNP genotypes as well as gut microbiome and phenotype data were obtained from the Kiel IBD family cohort (IBD-KC). The IBD-KC is an ongoing prospective study in Germany currently comprising 256 families with 455 IBD patients and 575 first- and second-degree relatives. Initially focusing upon known IBD risk loci, we noted a statistically significant (FDR<0.05) association between genetic similarity at SNP rs11741861 and overall microbiome dissimilarity among pairs of relatives discordant for IBD. In a genome-wide QTL analysis, 12 chromosomal regions were found to be linked to the abundance of one of seven microbial genera, namely Barnesiella (chromosome 4, region spanning 10.34 cM), Clostridium_XIVa (chr4, 3.86 cM; chr14, two regions spanning 7.05 and 13.02 cM respectively), Pseudoflavonifractor (chr7, 12.80 cM) Parasutterella (chr14, 8.26 cM), Ruminococcus (chr16, two overlapping regions spanning 8.01 and 16.87 cM, respectively), Roseburia (chr19, 7.99 cM), and Odoribacter (chr22, three regions spanning 0.89, 5.57 and 1.71 cM, respectively), as well as the Shannon index of α diversity (chr3, 1.47 cM). Our study thus shows that, in families of IBD patients, pairwise genetic similarity for at least one IBD risk locus is associated with overall microbiome dissimilarity among discordant pairs of relatives, and that hitherto unknown genetic modifiers of microbiome traits are located in at least 12 human genomic regions.
format Online
Article
Text
id pubmed-8820822
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Taylor & Francis
record_format MEDLINE/PubMed
spelling pubmed-88208222022-02-08 Linkage analysis identifies novel genetic modifiers of microbiome traits in families with inflammatory bowel disease Sharma, Arunabh Szymczak, Silke Rühlemann, Malte Freitag-Wolf, Sandra Knecht, Carolin Enderle, Janna Schreiber, Stefan Franke, Andre Lieb, Wolfgang Krawczak, Michael Dempfle, Astrid Gut Microbes Research Paper Dysbiosis of the gut microbiome is a hallmark of inflammatory bowel disease (IBD) and both, IBD risk and microbiome composition, have been found to be associated with genetic variation. Using data from families of IBD patients, we examined the association between genetic and microbiome similarity in a specific IBD context, followed by a genome-wide quantitative trait locus (QTL) linkage analysis of various microbiome traits using the same data. SNP genotypes as well as gut microbiome and phenotype data were obtained from the Kiel IBD family cohort (IBD-KC). The IBD-KC is an ongoing prospective study in Germany currently comprising 256 families with 455 IBD patients and 575 first- and second-degree relatives. Initially focusing upon known IBD risk loci, we noted a statistically significant (FDR<0.05) association between genetic similarity at SNP rs11741861 and overall microbiome dissimilarity among pairs of relatives discordant for IBD. In a genome-wide QTL analysis, 12 chromosomal regions were found to be linked to the abundance of one of seven microbial genera, namely Barnesiella (chromosome 4, region spanning 10.34 cM), Clostridium_XIVa (chr4, 3.86 cM; chr14, two regions spanning 7.05 and 13.02 cM respectively), Pseudoflavonifractor (chr7, 12.80 cM) Parasutterella (chr14, 8.26 cM), Ruminococcus (chr16, two overlapping regions spanning 8.01 and 16.87 cM, respectively), Roseburia (chr19, 7.99 cM), and Odoribacter (chr22, three regions spanning 0.89, 5.57 and 1.71 cM, respectively), as well as the Shannon index of α diversity (chr3, 1.47 cM). Our study thus shows that, in families of IBD patients, pairwise genetic similarity for at least one IBD risk locus is associated with overall microbiome dissimilarity among discordant pairs of relatives, and that hitherto unknown genetic modifiers of microbiome traits are located in at least 12 human genomic regions. Taylor & Francis 2022-02-06 /pmc/articles/PMC8820822/ /pubmed/35129060 http://dx.doi.org/10.1080/19490976.2021.2024415 Text en © 2022 The Author(s). Published with license by Taylor & Francis Group, LLC. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Paper
Sharma, Arunabh
Szymczak, Silke
Rühlemann, Malte
Freitag-Wolf, Sandra
Knecht, Carolin
Enderle, Janna
Schreiber, Stefan
Franke, Andre
Lieb, Wolfgang
Krawczak, Michael
Dempfle, Astrid
Linkage analysis identifies novel genetic modifiers of microbiome traits in families with inflammatory bowel disease
title Linkage analysis identifies novel genetic modifiers of microbiome traits in families with inflammatory bowel disease
title_full Linkage analysis identifies novel genetic modifiers of microbiome traits in families with inflammatory bowel disease
title_fullStr Linkage analysis identifies novel genetic modifiers of microbiome traits in families with inflammatory bowel disease
title_full_unstemmed Linkage analysis identifies novel genetic modifiers of microbiome traits in families with inflammatory bowel disease
title_short Linkage analysis identifies novel genetic modifiers of microbiome traits in families with inflammatory bowel disease
title_sort linkage analysis identifies novel genetic modifiers of microbiome traits in families with inflammatory bowel disease
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8820822/
https://www.ncbi.nlm.nih.gov/pubmed/35129060
http://dx.doi.org/10.1080/19490976.2021.2024415
work_keys_str_mv AT sharmaarunabh linkageanalysisidentifiesnovelgeneticmodifiersofmicrobiometraitsinfamilieswithinflammatoryboweldisease
AT szymczaksilke linkageanalysisidentifiesnovelgeneticmodifiersofmicrobiometraitsinfamilieswithinflammatoryboweldisease
AT ruhlemannmalte linkageanalysisidentifiesnovelgeneticmodifiersofmicrobiometraitsinfamilieswithinflammatoryboweldisease
AT freitagwolfsandra linkageanalysisidentifiesnovelgeneticmodifiersofmicrobiometraitsinfamilieswithinflammatoryboweldisease
AT knechtcarolin linkageanalysisidentifiesnovelgeneticmodifiersofmicrobiometraitsinfamilieswithinflammatoryboweldisease
AT enderlejanna linkageanalysisidentifiesnovelgeneticmodifiersofmicrobiometraitsinfamilieswithinflammatoryboweldisease
AT schreiberstefan linkageanalysisidentifiesnovelgeneticmodifiersofmicrobiometraitsinfamilieswithinflammatoryboweldisease
AT frankeandre linkageanalysisidentifiesnovelgeneticmodifiersofmicrobiometraitsinfamilieswithinflammatoryboweldisease
AT liebwolfgang linkageanalysisidentifiesnovelgeneticmodifiersofmicrobiometraitsinfamilieswithinflammatoryboweldisease
AT krawczakmichael linkageanalysisidentifiesnovelgeneticmodifiersofmicrobiometraitsinfamilieswithinflammatoryboweldisease
AT dempfleastrid linkageanalysisidentifiesnovelgeneticmodifiersofmicrobiometraitsinfamilieswithinflammatoryboweldisease