Multispecies, Integrative GWAS for Focal Segmental Glomerulosclerosis
Technical Report,15 Aug 2016,14 Aug 2017
Trustees of Columbia University New York United States
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Primary idiopathic nephrotic syndrome NS caused by focal segmental glomerulosclerosis FSGS or minimal change disease MCD is a frequent cause of end-stage renal diseaseESRD. 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 OR1.57, 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.
- Medicine and Medical Research
- Genetic Engineering and Molecular Biology