dc.description.abstract | Blood urea nitrogen (BUN) is a key biomarker of kidney function, reflecting the balance between urea production and excretion. Elevated BUN levels are associated with impaired kidney function and serve as a diagnostic and prognostic indicator for chronic kidney disease (CKD). CKD is an increasing public health concern in African populations, where the burden of kidney disease is compounded by genetic diversity, limited healthcare access, and rising prevalence of risk factors such as hypertension and diabetes. In this genome-wide association study (GWAS), we investigated the genetic architecture of BUN in 5,910 participants from the Uganda Genome Resource (UGR) cohort.Using the Genome-wide Efficient Mixed Model Association (GEMMA) to account for population structure and relatedness, we identified 13 SNPs with suggestive associations (p < 5x10^-7), five of which were independent lead SNPs. rs73309776 in the GALNT6 gene previously implicated in breast cancer may influence kidney function through cholesterol-related pathways. Another lead variant, rs145326389 in LOC105374218, suggests a potential role in blood pressure regulation via the renin-angiotensin-aldosterone system (RAAS) pathway. Replication of results in independent cohorts was followed by fine mapping using Bayesian fine mapping techniques, which helped pinpoint likely causal variants with higher resolution. Functional annotation revealed elevated expression of these genes in kidney-related tissues including the pituitary gland and kidney medulla supporting the role of BUN in CKD pathophysiology. Our findings provide novel insights into the genetic determinants of BUN in African populations. This is the first continental BUN GWAS and it has shown potential for explaining the genetic underpinnings of kidney functioning. We therefore recommend more studies involving continental Africans to streamline the genetic underpinnings of kidney function as this will give more strength to personalized medications and interventions for kidney treatments among them. | en_US |