Comprehensive Characterisation of the Nigerian Human Microbiome and Its Association with Genetic Variation: A Population Genomics Perspective

The human gut microbiome is shaped by both environmental factors and host genetic variation, yet microbiome-genome interaction studies have been conducted almost exclusively in European and East Asian populations. Nigeria's extraordinary human genetic diversity and unique dietary and ecological environments offer an unprecedented opportunity to characterise host genetics-microbiome interactions across diverse populations. This dissertation conducted comprehensive characterisation of the gut microbiome and its association with host genetic variation in 1,000 healthy adult Nigerians from across all six geopolitical zones. Faecal samples were collected for shotgun metagenomic sequencing on the Illumina NovaSeq platform. Host genomic data were generated using the H3Africa array. Microbiome composition, diversity, and functional pathway profiles were determined using MetaPhlAn3 and HUMAnN3. Genome-wide microbiome association studies (MiWAS) were conducted to identify host genetic loci associated with specific microbial taxa abundances and functional modules. The LCT gene region (lactase persistence) showed the strongest association with Bifidobacterium abundance across ethnic groups with differing dairy consumption traditions. Novel associations between HLA region variants and Akkermansia muciniphila abundance were identified. This dissertation establishes the first Nigerian human microbiome reference dataset and advances the global diversity of host genetics-microbiome interaction knowledge. Keywords: gut microbiome, host genetics, MiWAS, Nigerian population, metagenomics