Common Risk Variants in Are Associated With Childhood Steroid Sensitive Nephrotic Syndrome.

INTRODUCTION

Steroid-sensitive nephrotic syndrome (SSNS) is the most common form of kidney disease in children worldwide. Genome-wide association studies (GWAS) have demonstrated the association of SSNS with genetic variation at and have identified several non- loci that aid in further understanding of disease pathophysiology. We sought to identify additional genetic loci associated with SSNS in children of Sri Lankan and European ancestry.

METHODS

We conducted a GWAS in a cohort of Sri Lankan individuals comprising 420 pediatric patients with SSNS and 2339 genetic ancestry matched controls obtained from the UK Biobank. We then performed a transethnic meta-analysis with a previously reported European cohort of 422 pediatric patients and 5642 controls.

RESULTS

Our GWAS confirmed the previously reported association of SSNS with (rs9271602,  = 1.12 × 10, odds ratio [OR] = 2.75). Transethnic meta-analysis replicated these findings and identified a novel association at (rs2746432,  = 2.79 × 10, OR = 1.37), which was also replicated in an independent South Asian cohort. is implicated in ciliary protein transport and immune dysregulation, with rare variation in this gene contributing to Joubert syndrome type 3.

CONCLUSIONS

Common variation in confers risk of the development of SSNS in both Sri Lankan and European populations. The association with common variation in further supports the role of immune dysregulation in the pathogenesis of SSNS and demonstrates that variation across the allele frequency spectrum in a gene can contribute to disparate monogenic and polygenic diseases.