Characterizing the Genetic Architecture of Chronic Kidney Disease in the Australia’s First Peoples Using Statistical Methods

Chronic kidney disease (CKD) poses a substantial health burden among Indigenous Australians, particularly the Tiwi people. This thesis investigates the genetic architecture of CKD in the Tiwi population using whole-genome sequencing. Genome-wide association analyses identified population-specific loci associated with kidney traits, including MEG3, TIAM2, RAB36, and MEIS2. Runs of homozygosity analyses demonstrated elevated autozygosity and suggested a recessive contribution to albuminuria risk, with regional signals implicating FTO/CRNDE. Rare-variant analyses identified gene-based associations involving PCLO, TSPYL1, CYP4F22, and GCM2 with kidney-related and metabolic traits. Together, these findings advance understanding of CKD genetics in a genetically distinct and understudied population.