Accession Number : AD1045689

Title :   Multispecies, Integrative GWAS for Focal Segmental Glomerulosclerosis

Descriptive Note : Technical Report,15 Aug 2016,14 Aug 2017

Corporate Author : Trustees of Columbia University New York United States

Personal Author(s) : Sanna-Cherchi, Simone

Full Text :

Report Date : 01 Sep 2017

Pagination or Media Count : 16

Abstract : Primary idiopathic nephrotic syndrome (NS) caused by focal segmental glomerulosclerosis (FSGS) or minimal change disease (MCD) is a frequent cause of end-stage renal disease(ESRD. We investigated the genetic basis of FSGS and recruited a heterogeneous population of Caucasian descent ascertained for FSGS (88 of the cases) and MCD (12 ), for a total of 1,153 cases. A set of independent and meta-analyzed case-control, genome-wide association studies (GWAS) were performed using an additive model with covariate correction for population stratification in Quality control assessment was carried out according to standard practices. In a Meta-analysis of three, combined Caucasian cohorts (1153cases, 2393 controls), a significant association was found for the SNP rs28383303 (OR=1.57, 95 CI: 1.29-1.67, P= 1.48x10-8). The variant was identified in a 50kb haploblock on chromosome 6p21, which contains the gene encoding the HLA complex class II HLA-DQ alpha chain 1 (HLA-DQA1). In line with previously reported findings implicating the HLA system in childhood-onset nephrotic syndrome and membranous nephropathy, our results indicate the association of HLA risk alleles with NS in individuals of Caucasian descent. Our findings allude to a role for HLA in modulating adaptive immunity and suggest a basis for understanding the complex genetic mechanisms of FSGS.

Descriptors :   KIDNEY DISEASES , genetics , genomics , CAUCASIANS

Subject Categories : Medicine and Medical Research
      Genetic Engineering and Molecular Biology

Distribution Statement : APPROVED FOR PUBLIC RELEASE