ARCTIC · Assessing diabetes and obesity risk through causal biomarkers from host proteogenomic and gut microbiome in Greenlandic Inuit

Diabetes and obesity incidences are rising globally, yet precision medicine solutions remain scarce. The Greenlandic Inuit population carries a unique genetic background with increased diabetes risk, but type-2-diabetes (T2D) is substantially underdiagnosed due to distinct disease pathology and biomarker profiles. The proteome and microbiome provide powerful intermediate readouts of genetic regulation, disease mechanisms, environmental factors, and lifestyle. Both have been linked to T2D and obesity in general populations. In the interdisciplinary ARCTIC project, I will integrate the unique genetic background of Greenlandic Inuit (n=4180) with their plasma proteomics, fecal metagenomics, anthropometric, biochemical, clinical, and health registry data. The project aims to uncover diagnostic and prognostic biomarkers as well as the causal pathways of T2D and obesity. By leveraging plasma proteomics (>1200 proteins, 4180 samples) and the first-ever human fecal metagenomic sequencing effort in Greenland (700 samples), I will identify circulating proteins and microbial features that predict disease and incidence. Using genotyping information, I will locate protein quantitative trait loci (pQTLs) and assess their genetic colocalization with obesity and T2D risk variants to identify causal proteins, genes, and pathways. By integrating individual-level plasma proteomics and fecal microbiome profiles with host genetics and clinical data, I will enhance our understanding of the host-microbe symbiosis mechanisms and their interplay in disease. The ARCTIC project will help reduce inequity in clinical care by advancing precision medicine for T2D and obesity in the Greenlandic population. It will provide new therapeutic targets for both indigenous and global populations and enhance our understanding of the host–microbe interactions that drive disease.