Multiethnic Integrated GWAS to Illuminate the Pathobiology of FSGS
Abstract
Overarching Challenge: This project directly addresses the FY21 PRMP area Focal Segmental Glomerulosclerosis. FSGS is a common form of kidney injury and a major cause of end-stage kidney disease (ESKD). It is particularly common among people of recent African ancestry. FSGS is not one disease, but rather a collection of entities with a similar histologic phenotype. There has been considerable progress in understanding the genetic basis of FSGS over the past two decades. Still, the underlying pathobiology of disease is largely obscure, and therapeutic options are limited. Until now there has not been a coordinated effort to pull together investigators, resources, and patient populations to tackle this problem using a genome-wide association (GWAS) approach. No studies also have combined large-scale genetics with mouse genetics and transcriptomic analyses. Thus, we are proposing a comprehensive approach to dissecting the complex molecular and genetic basis of focal segmental glomerulosclerosis (FSGS)Background: FSGS is a common pattern of kidney injury in both adults and children. Over the past years, there have been large advances in understanding the genetic basis of FSGS. However, in the majority of cases, even when a positive family history is present, mutations in a known FSGS gene cannot be identified. The role of copy number variations (CNVs) and common variants with small to moderate effect size is poorly understood. In fact, no GWAS have been conducted for this trait so far. An improved understanding of the genetic architecture of FSGS is expected to lead to marked improvements in its diagnosis and ultimately its therapy. Research Plan: This research program will consist of three independent but highly interrelated Aims. The principal goal here is to assess the contribution of common genetic variants to FSGS and how they relate to rare point mutations and CNVs.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2023
- Accession Number
- AD1221810
Entities
People
- Simone Sanna-cherchi
Organizations
- Columbia University