As a complementary approach for identifying genetic determinants of DN susceptibility, we will take advantage of our whole genome sequence (WGS) datasets in diabetic subjects from European (Finnish) and multi-ethnic Singaporean cohorts, as well as from our unique mouse model of DN, to identify genes and pathways affecting DN susceptibility. We will integrate genomic analyses across these multiple systems, use a multi-level “functional screening approach” to validate in vivo candidate genes, adopting multi-ancestry genome-wide mapping using WGS data in the Chinese and Malay DN cohorts, and as described in Theme 4. Genes identified in DN patients and in the mouse model will be tested in vivo in Drosophila and transgenic mice, and in kidney organoids by an integrated and high-throughput functional screening approach. They will also be correlated with results from GWAS in Theme 4.