Abstract: FR-OR034

Glomerular and Tubulointerstitial eQTLs of Patients with Nephrotic Syndrome

Session Information

Category: Genetic Diseases of the Kidney

  • 803 Genetic Epidemiology and Other Genetic Studies of Common Kidney Diseases


  • Putler, R, University of Michigan, Ann Arbor, Michigan, United States
  • Wen, Xiaoquan, University of Michigan, Ann Arbor, Michigan, United States
  • Sampson, Matt G., University of Michigan, Ann Arbor, Michigan, United States

Group or Team Name


Using intrarenal mRNA expression as a molecular phenotype in expression quantitative trait loci (eQTL) studies of nephrotic syndrome (NS) can lead to discovery of transcripts under significant genetic control, reveal novel NS-related biology, and identify loci associated with clinically meaningful outcomes. To describe the intrarenal eQTL landscape of NS, we paired whole genome sequencing with glomerular (GLOM) & tubulointerstitial (TI) transcriptomes from patients in the Nephrotic Syndrome Study Network (NEPTUNE).


NEPTUNE is a prospective, longitudinal study of NS enrolling affected adults and children receiving a clinically indicated biopsy. Rich demographic, clinical, and genomic data is collected and GLOM & TI transcriptomes are derived from a microdissected research biopsy core. We performed a cis-eQTL study to identify GLOM & TI transcripts under genetic regulation by SNPs within 1Mb of the gene. We used the Bayesian “Deterministic Approximation of Posteriors” (DAP), which uses linkage disequilibrium and annotation information, to discover & fine-map eQTL signals within each locus while controlling for multiple testing. We included appropriate covariates for each dataset. We utilized MatrixEQTL for the same data to gain insight into direction of effect for these signals.


At genome-wide significance, we discovered 340 independent eQTL signals in 313 unique genes in GLOM and 862 independent signals in 772 unique genes in TI. PLCG2, previously implicated in steroid sensitive NS via burden testing, was one of the strongest GLOM eQTLs. Five of 30 Mendelian NS genes had both a GLOM eQTL and a significant association with eGFR. This suggests that non-coding variants regulating Mendelian NS gene expression can impact clinical outcomes. 14% and 28% of significant eQTLs were GLOM- and TUB-specific, respectively. 58% of eQTLs were shared between GLOM & TI. When we compared the significance of GLOM- & TI-eQTLs with blood-derived eQTLs (from GTeX), 19% of eQTLs had more significant minimum p-value in GLOM & TI vs blood, despite smaller sample size.


In our glomerular & tubulointerstitial eQTL study of NS patients, we discovered 100s of genes under significant genetic control. We can now pursue their biologic & clinical correlates. Making this NS eQTL database publicly available should be a useful resource to inform future molecular & epidemiologic studies of NS.


  • NIDDK Support