Approved Research

Genetic architecture of chronic disease in multi-ethnic populations

Lay summary

Indigenous Australian populations suffer disproportionately from chronic kidney disease (CKD) and other severe chronic diseases, with the significant gap in life expectancies between Indigenous and non-Indigenous Australian populations being largely attributable to chronic disease-related mortality. Despite major advances in the fields of genetics, pharmacogenomics, and transfusion medicine in recent decades, Indigenous populations remain underrepresented in genomic datasets and studies, and thus fail to benefit from these potentially life-saving breakthroughs.

In this proposed 36-month project, we will use our Indigenous Australian datasets to identify genetic variants associated with clinically important outcomes, with the UK Biobank datasets serving as a reference population and enabling us to detect variants of interest in these Indigenous founder populations.

Through the proposed analyses, we expect to accomplish three specific project aims. First, we will seek to identify disease-causing genes associated with chronic diseases. The successful identification of these genetic targets will offer new insights regarding the basic biology of chronic disease while also defining new targets that may be specifically relevant to preventative or therapeutic intervention efforts in Indigenous populations. Second, we will attempt to define pharmacogenomics markers associated with chronic disease. These genetic variants, which affect the safety and efficacy of specific drugs, will enable the more reliable treatment of Indigenous individuals suffering from CKD and other chronic conditions while reducing the risk of treatment-related adverse events. Third, we will establish the blood group antigens that are present in Indigenous Australian populations, as the identification of these antigens will support more comprehensive donor matching, lowering the risk of negative outcomes in Indigenous patients receiving blood transfusions or transplanted organs.

Together, the results of this project will identify readily actionable genetic variants with the potential to guide prevention, treatment, and monitoring efforts for Indigenous Australian populations suffering from CKD and other chronic diseases, thereby helping to close the mortality gap by ensuring more equitable access to personalized medicine.