Preprint Article Version 1 This version is not peer-reviewed

A Two-Sample Mendelian Randomization Analysis Investigates Associations between Gut Microbiota and Celiac Disease

Version 1 : Received: 25 March 2020 / Approved: 26 March 2020 / Online: 26 March 2020 (14:08:31 CET)

A peer-reviewed article of this Preprint also exists.

García-Santisteban, I.; Cilleros-Portet, A.; Moyua-Ormazabal, E.; Kurilshikov, A.; Zhernakova, A.; Garcia-Etxebarria, K.; Fernandez-Jimenez, N.; Bilbao, J.R. A Two-Sample Mendelian Randomization Analysis Investigates Associations Between Gut Microbiota and Celiac Disease. Nutrients 2020, 12, 1420. García-Santisteban, I.; Cilleros-Portet, A.; Moyua-Ormazabal, E.; Kurilshikov, A.; Zhernakova, A.; Garcia-Etxebarria, K.; Fernandez-Jimenez, N.; Bilbao, J.R. A Two-Sample Mendelian Randomization Analysis Investigates Associations Between Gut Microbiota and Celiac Disease. Nutrients 2020, 12, 1420.

Journal reference: Nutrients 2020, 12, 1420
DOI: 10.3390/nu12051420

Abstract

Celiac disease (CeD) is a complex immune-mediated inflammatory condition triggered by ingestion of gluten in genetically predisposed individuals. Literature suggests that alterations in gut microbiota composition and function precede the onset of CeD. Considering that microbiota is partly determined by host genetics, we speculate that the genetic makeup of CeD patients could elicit disease development through alterations in the intestinal microbiota. To evaluate potential causal relationships between gut microbiota and CeD, we performed a Two-Sample Mendelian Randomization analysis (2SMR). Exposure data were obtained from the raw results of a previous Genome Wide Association Study (GWAS) of gut microbiota, and outcome data from summary statistics of CeD GWAS and Immunochip studies. We have identified a number of putative associations between gut microbiota SNPs associated with CeD. Regarding bacterial composition, most of the associated SNPs are related to Firmicutes phylum, whose relative abundance has been previously reported to be altered in CeD patients. In terms of functional units, we have linked a number of SNPs to several bacterial metabolic pathways that seem to be related to CeD. Overall, this study represents the first 2SMR approach to elucidate the relationship between microbiome and CeD.

Subject Areas

celiac disease; gut microbiota; mendelian randomization

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