Publication

SLC39A8 missense variant is associated with Crohn's disease but does not have a major impact on gut microbiome composition in healthy subjects

Collij, V., Imhann, F., Vich Vila, A., Fu, J., Dijkstra, G., Festen, E. A. M., Voskuil, M. D., Daly, M. J., Xavier, R. J., Wijmenga, C., Zhernakova, A. & Weersma, R. K., 31-Jan-2019, In : PLoS ONE. 14, 1, 13 p., 0211328.

Research output: Contribution to journalArticleAcademicpeer-review

Background

Gene-microbiome interactions are important in aetiology and pathogenesis of inflammatory bowel disease, a chronic inflammatory disorder of the gastrointestinal tract consisting of Crohn's disease and ulcerative colitis. Scarce studies on gene-microbiome interactions show very little overlap in their results. Therefore, it is of utmost importance that gene-microbiome studies are repeated. We aimed to replicate the association between the SLC39A8[Thr]391 risk allele and gut microbiome composition in patients with inflammatory bowel disease and healthy controls.

Methods

We collected faecal samples, peripheral blood and extensive phenotype data from 291 patients with inflammatory bowel disease and 476 healthy controls. Carrier status information was obtained from whole exome sequencing data, generated using the Illumina HiSeq. The gut microbiome composition was determined by tag-sequencing the 16S rRNA gene. Associations between carrier status and disease were tested using the Wilcoxon-Mann-Whitney test. Associations between carriers and gut microbiome composition were determined using principal coordinate analyses, variance explained, alpha diversity and additive general linear models in inflammatory bowel disease, healthy controls and all groups combined.

Results

Crohn's disease patients were more often carriers of the missense variant (21/171, 12.3%) than controls (30/476, 6.3%) (OR = 2.1, P = 0.01). We could not identify associations between carrier status and overall gut microbiome composition and microbial richness in all tested groups after correcting for potential confounding factors. We did identify 37 different operational taxonomical units to be associated with carrier status among the tested groups. Two of these 37 were identified before in the discovery study.

Conclusions

We could confirm the genetic association of the SLC39A8[Thr]391 risk allele with Crohn's disease but we could only limited replicate the association in gut microbiome composition. Independent replication of gene-microbiome studies is warranted to identify true biological mechanisms.

Original languageEnglish
Article number0211328
Number of pages13
JournalPLoS ONE
Volume14
Issue number1
Publication statusPublished - 31-Jan-2019

    Keywords

  • INFLAMMATORY-BOWEL-DISEASE, GENOME, ZINC

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