Interplay between host genetics and gut microbiome composition in the Japanese population.

Background: Host genetics significantly influence the composition of the gut microbiota, but this relationship remains poorly understood, especially in non-European populations. This study aims to investigate the associations between host genetic variation and gut microbiome composition in the Japanese population and to assess methodological factors affecting reproducibility in microbiome research. Methods: We performed whole-genome sequencing on 306 Japanese individuals and obtained their gut microbiome profiles using shotgun metagenomic sequencing. Genome-wide association studies (GWAS) were conducted to identify associations between host genetic variants and the relative abundance of microbial taxa and bacterial pathways. Phenome-wide association studies (PheWAS) were performed on predicted high-impact variants. Additionally, we compared methodological approaches to assess their impact on microbiome composition and reproducibility. Results: We identified significant associations between host genetic variants and the relative abundance of one bacterial family, one genus, one species and eight bacterial pathways ( Conclusion: Our findings enhance the understanding of how host genetics shape the gut microbiota in the Japanese population and underscore the importance of methodological standardization in microbiome research. The identified associations between host genetic variants and specific microbial taxa provide insights into the complex interplay between genetics and the gut microbiome. Addressing methodological discrepancies is crucial for improving reproducibility and advancing knowledge of host-microbiome interactions.