Enrichment of Transcriptional Regulators at Steroid Sensitive Nephrotic Syndrome Genetic Risk Loci

Enrichment of Transcriptional Regulators at Steroid Sensitive Nephrotic Syndrome Genetic Risk Loci

Bibliographic Details
Main Author: Stone, Hillarey
Language:English
Published: University of Cincinnati / OhioLINK 2020
Subjects:
Surgery
nephrotic syndrome
genetics
transcription factors
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=ucin160199291391191
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spelling ndltd-OhioLink-oai-etd.ohiolink.edu-ucin1601992913911912021-10-02T05:10:33Z Enrichment of Transcriptional Regulators at Steroid Sensitive Nephrotic Syndrome Genetic Risk Loci Stone, Hillarey Surgery nephrotic syndrome genetics transcription factors Introduction: The etiology of steroid sensitive nephrotic syndrome (SSNS) is not well understood. Genetic studies have established common single nucleotide polymorphisms (SNPs) that are associated with increased SSNS disease risk. We review previous genetic association studies of SSNS and nominate particular transcriptional regulators and immune cells as potential key players in the etiology of this disease.Methods: A list of SNPs associated with SSNS was compiled from published genome wide association and candidate gene studies. The Regulatory Element Locus Intersection (RELI) tool was used to calculate the enrichment of the overlap between disease risk SNPs and the genomic coordinates of data from a collection of >10,000 chromatin immunoprecipitation (ChIP-seq) experiments.Results: After linkage disequilibrium expansion of the previously reported tag associated SNPs, we identified 192 genetic variants at 8 independent risk loci. Using the RELI algorithm, we identified transcriptional regulators with enriched binding at SSNS risk loci (10-05 < pcorrected < 10-124), including ZNF530, CIITA, CD74, RFX5, and ZNF425. Many of these regulators have well-described roles in the immune response. RNA polymerase II binding in B cells also demonstrated enriched binding at SSNS risk loci (10-37<pcorrected<10-5).Conclusion: SSNS is a complex disease, and immune dysregulation has been previously implicated as a potential underlying cause. This assessment of established SSNS risk loci and analysis of possible function implicates transcriptional dysregulation, and specifically particular transcriptional regulators with known roles in the immune response, as important in the genetic etiology of SSNS. 2020 English text University of Cincinnati / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=ucin160199291391191 http://rave.ohiolink.edu/etdc/view?acc_num=ucin160199291391191 unrestricted This thesis or dissertation is protected by copyright: some rights reserved. It is licensed for use under a Creative Commons license. Specific terms and permissions are available from this document's record in the OhioLINK ETD Center.
collection NDLTD
language English
sources NDLTD
topic Surgery
nephrotic syndrome
genetics
transcription factors
spellingShingle Surgery
nephrotic syndrome
genetics
transcription factors
Stone, Hillarey
Enrichment of Transcriptional Regulators at Steroid Sensitive Nephrotic Syndrome Genetic Risk Loci
author Stone, Hillarey
author_facet Stone, Hillarey
author_sort Stone, Hillarey
title Enrichment of Transcriptional Regulators at Steroid Sensitive Nephrotic Syndrome Genetic Risk Loci
title_short Enrichment of Transcriptional Regulators at Steroid Sensitive Nephrotic Syndrome Genetic Risk Loci
title_full Enrichment of Transcriptional Regulators at Steroid Sensitive Nephrotic Syndrome Genetic Risk Loci
title_fullStr Enrichment of Transcriptional Regulators at Steroid Sensitive Nephrotic Syndrome Genetic Risk Loci
title_full_unstemmed Enrichment of Transcriptional Regulators at Steroid Sensitive Nephrotic Syndrome Genetic Risk Loci
title_sort enrichment of transcriptional regulators at steroid sensitive nephrotic syndrome genetic risk loci
publisher University of Cincinnati / OhioLINK
publishDate 2020
url http://rave.ohiolink.edu/etdc/view?acc_num=ucin160199291391191
work_keys_str_mv AT stonehillarey enrichmentoftranscriptionalregulatorsatsteroidsensitivenephroticsyndromegeneticriskloci
_version_ 1719486486648193024

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