Multispecies, Integrative GWAS for Focal Segmental Glomerulosclerosis
Abstract
Focal Segmental Glomerulosclerosis (FSGS) is one of the most common causes of nephrotic syndrome and several studies reported an increase of FSGS diagnosis with up to 18.7% and 47% of cases in adults and children receiving a kidney biopsy, respectively. From a clinical perspective, idiopathic FSGS is characterized by high morbidity, poor response to medical therapy, and high rate of progression to end-stage renal disease requiring dialysis or transplantation. We approached this phenotype in a comprehensive fashion using both human genetics and mouse studies. In a human GWAS of FSGS, we detected genome-wide significant signals in the in the HLA and APOL1 loci, as well as in multiple novel loci after analysis of subgroups of FSGS stratified by age of onset and response to immunosuppressive therapy. In a mouse model of collapsing FSGS, we detected a signal on Chr13. Fine mapping studies and bioinformatics analyses suggested Ssbp2 as the lead candidate. Analysis of Ssbp2 null mice demonstrated that they develop spontaneous FSGS with aging. These data identify multiple risk loci and candidate genes for FSGS in human and mice and implicate new pathways in disease pathogenesis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2020
- Accession Number
- AD1133868
Entities
People
- Ali G. Gharavi
- Simone Sanna-cherchi
Organizations
- Columbia University