Dissecting the Genetic Architecture of Cystatin C in Diversity Outbred Mice-Reference-Cited by-同舟云学术

Dissecting the Genetic Architecture of Cystatin C in Diversity Outbred Mice

Published:2020-07-01 Issue:7 Volume:10 Page:2529-2541
ISSN:2160-1836
Container-title:G3 Genes|Genomes|Genetics
language:en
Short-container-title:

Author:

Huda M Nazmul¹²^ORCID,VerHague Melissa³,Albright Jody⁴,Smallwood Tangi⁴,Bell Timothy A⁴,Que Excel¹,Miller Darla R⁴,Roshanravan Baback⁵,Allayee Hooman⁶,Manuel de Villena Fernando Pardo⁴^ORCID,Bennett Brian J¹²

Affiliation:

1. Obesity and Metabolism Research Unit, Western Human Nutrition Research Center, USDA, ARS, Davis, California 95616

2. Department of Nutrition, University of California Davis, California 95616

3. Nutrition Research Institute, University of North Carolina Kannapolis, North Carolina 28081

4. Department of Genetics, University of North Carolina at Chapel Hill, North Carolina 27599

5. Department of Medicine, Division of Nephrology, University of California, Davis, Davis, California 95616, and

6. Departments of Preventive Medicine and Biochemistry & Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles California 90033

Abstract

Abstract Plasma concentration of Cystatin C (CysC) level is a biomarker of glomerular filtration rate in the kidney. We use a Systems Genetics approach to investigate the genetic determinants of plasma CysC concentration. To do so we perform Quantitative Trait Loci (QTL) and expression QTL (eQTL) analysis of 120 Diversity Outbred (DO) female mice, 56 weeks of age. We performed network analysis of kidney gene expression to determine if the gene modules with common functions are associated with kidney biomarkers of chronic kidney diseases. Our data demonstrates that plasma concentrations and kidney mRNA levels of CysC are associated with genetic variation and are transcriptionally coregulated by immune genes. Specifically, Type-I interferon signaling genes are coexpressed with Cst3 mRNA levels and associated with CysC concentrations in plasma. Our findings demonstrate the complex control of CysC by genetic polymorphisms and inflammatory pathways.

Publisher

Oxford University Press (OUP)

Subject

Genetics (clinical),Genetics,Molecular Biology

Link

http://academic.oup.com/g3journal/article-pdf/10/7/2529/40667722/g3journal2529.pdf

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