Manuscript accepted in Nature Communications

The manuscript titled "Novel insights into the genetic architecture and mechanisms of host/microbiome interactions from a multi-cohort analysis of outbred laboratory rats" was accepted in Nature Communications.

Authors: Helene Tonnele, Denghui Chen, Felipe Morillo, Jorge Garcia-Calleja, Apurva S Chitre, Benjamin B Johnson, Thiago Missfeldt Sanches, Marc Jan Bonder, Antonio Gonzalez, Tomasz Kosciolek, Anthony M George, Wenyan Han, Katie Holl, Aidan Horvath, Keita Ishiwari, Christopher P King, Alexander C Lamparelli, Connor D Martin, Angel Garcia Martinez, Alesa H Netzley, Jordan A Tripi, Tengfei Wang, Elena Bosch, Peter A Doris, Oliver Stegle, Hao Chen, Shelly B Flagel, Paul J Meyer, Jerry B Richards, Terry E Robinson, Leah C Solberg Woods, Oksana Polesskaya, Rob Knight, Abraham A Palmer, Amelie Baud.

(Current Palmer Lab members)

Congratulations!

Nature Communications, 2025, Dec 18;16(1):10126

DOI: https://doi.org/10.1038/s41467-025-66105-z

Figure 4: Microbiome-associated loci. This porcupine plot shows the association values for all microbiome phenotypes (n = 2,294 phenotypes from 4 cohorts). The lower line (-logP = 5.8) reflects the genome-wide significance threshold for an individual trait, which accounts for the number of independent SNPs tested; the higher line (-logP = 8.4) is the adjusted significance threshold, which in addition accounts for the number of independent microbiome phenotypes examined in each cohort. The larger, colored dots highlight genome-wide significant associations for microbiome phenotypes that have an annotation at the genus level. The color of the dot refers to the genus affected. The shape of the dot refers to the cohort in which the association was identified.

Fig. 5: Dissection of the mechanisms underlying the replicated association between Paraprevotella and the St6galnac1 locus on chromosome 10. A) Local association (LocusZoom) plot for ASV_5163 (genus Paraprevotella) measured in the NY cohort and the St6galnac1 locus. Eight genes were omitted for graphical purposes. The y-axis shows the −log₁₀ p-value from an LRT with one degree of freedom comparing a model with a fixed effect for the tested SNP to a null model without (see “Methods” section on GWAS). A wider plot is shown in Supplementary Fig. 11. B) Alignment of Illumina short reads from the eight founders of the HS population to the rat reference genome assembly (rn7). C) Comparison of the rat reference genome assembly (rn7, from strain BN/NHsdMcwi) and the de novo genome assembly of the strain SHRSP/BbbUtx, which is identical by descent to WN/N at the locus. D–F) Genotypic effects on Paraprevotella, A. muciniphila and M. intestinale ASVs that map to the St6galnac1 locus (see Supplementary Table 4). A few outliers were omitted for better visualisation of the quartiles. Given the very small number of rats that were homozygous for the triplication, the association is driven by the difference between the other two genotype groups.

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