Article
Can genetic similarity explain microbiome similarity in Inflammatory Bowel Diseases?
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Authors
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Arunabh Sharma
- Christian-Albrechts-Universität zu Kiel, Kiel, Germany
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Sandra Freitag-Wolf
- Christian-Albrechts-Universität zu Kiel, Kiel, Germany
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Michael Krawczak
- Christian-Albrechts-Universität zu Kiel, Kiel, Germany
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Astrid Dempfle
- Christian-Albrechts-Universität zu Kiel, Kiel, Germany
| Published: | February 26, 2021 |
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Outline
Text
Background: Over 200 inflammatory bowel diseases risk loci have been identified [1]. Several studies aim to find a connection between the host microbiome and inflammatory bowel diseases. In family-based designs, one can leverage the amount of shared genetic material to a phenotype of interest.
Methods: Here, we investigated the association between genetic similarity and microbiome similarity using genetic and microbiome data from the inflammatory bowel disease family-cohort KINDRED, which recruited currently unaffected family members of patients. We used identity-by-descent (IBD) at risk loci between pairs of individuals as a measure of genetic similarity to explain similarity in microbiome for affected-unaffected pairs (discordant). As a first step, the multipoint IBD calculations were carried out using a region (500kb) flanking each risk SNP for all relative pairs in the dataset. Thereafter, we looked at the combined IBD values for all the risk SNPs for a pair of individuals and did an association testing with microbiome (beta diversity of all bacterial taxa) for that pair using several clinical features as model covariates. Using a stepwise model selection approach, we identified pair type (concordant/discordant for disease) and smoking status (smoker-non smoker) as the key confounders. This was followed by an analysis for every risk SNP individually for all pair types while considering bacterial phyla frequently reported in the literature for inflammatory bowel diseases. Going a step further, we also analysed only discordant pairs.
Results: In our preliminary results, we observe that the risk loci rs4722672, rs10486483, rs3749171 and rs864745 are significantly associated with the phylum ‘Bacteroidetes’ (FDR <0.05) while looking at all the pairs.
Conclusion: The risk SNPs significantly associated with the Bacteroidetes suggests an association between genetic similarity and microbiome similarity in inflammatory bowel diseases while looking at all the pairs.
The authors declare that they have no competing interests.
The authors declare that an ethics committee vote is not required.
References
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