Lay summary
Diabetic kidney disease is a major health issue in New Zealand. Māori and Pacific people are particularly affected, with genetics being a likely component of this inequity. We have identified a DNA variant in the CALCRL gene that is common in people with Eastern Polynesian ancestry (including Māori) but is rare outside of Oceania. This variant causes CALCRL, a receptor involved in lipid metabolism, blood pressure and insulin regulation, to be hyperactive and is linked to high cholesterol and more severe kidney disease in individuals with diabetes. Here, we will study the biological consequences of the CALCRL variant by examining its effect in several different human populations and via a gene-edited rat carrying the variant. This work will further our understanding of the genetic contributors of diabetic kidney disease, help reduce health inequities, and lay the foundations for developing precision medicine approaches that are tailored to Māori.