Defining Causal Variants and Associated Genes in Polygenic Nephrolithiasis

Kidney stones are a common problem. Unfortunately, the causes of kidney stone formation are poorly understood, stones are frequently recurrent, and prevention strategies are relatively ineffective. I have identified 20 areas on the genome (loci) that are linked to stone formation but it is not known what effects variations in DNA sequence at these loci are having on how genes are converted to proteins and on biological pathways. The aim of my project is to link these loci of interest to cellular function. I will do this by looking at the structure of DNA in different kidney cell types, using laboratory-based techniques to identify what effects genes of interest have on biological pathways, and studying how variations in DNA sequence associate with biological characteristics in people. These studies will help us understand the causes of kidney stone formation and identify targets for novel preventative drug therapies.