Identification of novel loci associated with human microbiota composition

Our understanding of the factors shaping intestinal microbiome composition has increased significantly during last decade. Host genetics is one of these factors and may explain ~10% of the microbiome variance . So far, and despite the number of GWAS studies performed to identify loci associated with microbiome composition, only few associations were cross‑replicated.

This study makes use of an extensive dataset integrating 300 healthy individuals (CEDAR-1 cohort) from whom we obtained (i) genotype (Illumina Human OmniExpress BeadChip imputed to 6M SNPs with MAF⩾5%) (ii) 16S rRNA based taxonomic assignation for biopsies from the ileum, transverse colon and rectum (3 amplicons mapped to SILVA database). We performed a GWAS (PLINK additive model) to unravel new associations between genotype and microbiota.

Our findings were further verified in two confirmation cohorts obtained from residual stool samples collected during colonoscopy (n=295), from ileum, transverse colon and rectum biopsies and stools (CEDAR-2 cohort) (n~ 50 and 20) where we also tested for individual variation regarding sample provenance.

We observed that intestinal location explained a small part of the microbiome variability (<1%) in our dataset. The variation in microbial composition explained by the individual effect represents the major fraction (>50%).

We identified three association between SNP and bacterium abundance at the experiment-wide p-value threshold (6x10-10). Among these three associations, the second and third were reproduced at nominal p value of 5% in the confirmation cohort.

We have identified 2 putative novel loci associated with human microbiome composition . We also showed a strong individual effect on bacterial communities and a low location variability across the intestinal tract.