Unravelling the complex genetics of common kidney diseases: from variants to mechanisms.

Nature Reviews. Nephrology
Katie Marie Sullivan, Katalin Susztak

Abstract

Genome-wide association studies (GWAS) have identified hundreds of loci associated with kidney-related traits such as glomerular filtration rate, albuminuria, hypertension, electrolyte and metabolite levels. However, these impressive, large-scale mapping approaches have not always translated into an improved understanding of disease or development of novel therapeutics. GWAS have several important limitations. Nearly all disease-associated risk loci are located in the non-coding region of the genome and therefore, their target genes, affected cell types and regulatory mechanisms remain unknown. Genome-scale approaches can be used to identify associations between DNA sequence variants and changes in gene expression (quantified through bulk and single-cell methods), gene regulation and other molecular quantitative trait studies, such as chromatin accessibility, DNA methylation, protein expression and metabolite levels. Data obtained through these approaches, used in combination with robust computational methods, can deliver robust mechanistic inferences for translational exploitation. Understanding the genetic basis of common kidney diseases means having a comprehensive picture of the genes that have a causal role in disease deve...Continue Reading

References

Feb 16, 2002·Science·Job DekkerNancy Kleckner
Apr 12, 2003·International Journal of Epidemiology·George Davey Smith, Shah Ebrahim
Oct 23, 2004·Science·Tomi Pastinen, Thomas J Hudson
Sep 20, 2005·Lancet·M Dawn Teare, Jennifer H Barrett
Jul 1, 2006·Genome Research·Batbayar KhulanJohn M Greally
Sep 22, 2007·Statistics in Medicine·Debbie A LawlorGeorge Davey Smith
Jun 5, 2008·European Journal of Human Genetics : EJHG·Astrid DempfleHelmut Schäfer
Apr 21, 2009·Methods in Molecular Biology·Manon GaudreaultSylvain L Guérin
May 12, 2009·Nature Genetics·Anna KöttgenCaroline S Fox
Jul 2, 2009·American Journal of Hematology·Paola SebastianiMartin H Steinberg
Jul 3, 2009·The New England Journal of Medicine·Laurence H BeckDavid J Salant
Sep 19, 2009·Methods in Molecular Biology·Lude Franke, Ritsert C Jansen
Dec 5, 2009·Journal of the American Society of Nephrology : JASN·Anna KöttgenCaroline S Fox
May 20, 2011·Epigenetics : Official Journal of the DNA Methylation Society·Juan SandovalManel Esteller
Sep 14, 2011·Methods in Molecular Biology·Henriette O'GeenPeggy J Farnham
Sep 22, 2011·Nature Immunology·Benjamin L KidderKeji Zhao
Dec 23, 2011·European Journal of Human Genetics : EJHG·Hae-Won UhJeanine J Houwing-Duistermaat
Jan 17, 2012·American Journal of Human Genetics·Peter M VisscherJian Yang
May 30, 2012·Nature Reviews. Genetics·Peter A Jones
Sep 8, 2012·Science·Matthew T MauranoJohn A Stamatoyannopoulos
Sep 8, 2012·Genome Research·Marc A SchaubMichael Snyder
Nov 6, 2012·Clinical Journal of the American Society of Nephrology : CJASN·Robert N Foley, Allan J Collins
Jan 19, 2013·Science·Cosmas D ArnoldAlexander Stark
Mar 19, 2013·Nature Reviews. Genetics·Len A PennacchioGill Bejerano
Apr 3, 2013·Current Protocols in Molecular Biology·Jeremy M SimonJason D Lieb
Jun 7, 2013·Journal of Human Genetics·Hiroshi Kimura
Aug 14, 2013·PLoS Biology·Christopher R BrownHinrich Boeger
Sep 6, 2013·Genome Research·Michael J FlisterCarol Moreno
Oct 26, 2013·Nature Protocols·F Ann RanFeng Zhang
Nov 2, 2013·Journal of the American Society of Nephrology : JASN·Katalin Susztak
Nov 5, 2013·Nature Biotechnology·Joshua N BurtonJay Shendure
Feb 5, 2014·Cold Spring Harbor Perspectives in Biology·Denise P Barlow, Marisa S Bartolomei
Feb 11, 2014·Nature Genetics·UNKNOWN DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) ConsortiumAndrew P Morris

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Citations

Oct 9, 2020·Nature Reviews. Nephrology·Markus M Rinschen, Julio Saez-Rodriguez
May 18, 2021·The Journal of Clinical Investigation·Tomohito DokeKatalin Susztak
Jul 9, 2021·Frontiers in Endocrinology·Vinay Singh TanwarRama Natarajan
Aug 22, 2021·Nature Reviews. Nephrology·Zhen MiaoJunhyong Kim
Sep 30, 2021·Nature Reviews. Nephrology·Adebowale A AdeyemoCharles N Rotimi

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Methods Mentioned

BETA
single-cell sequencing
exome sequencing
dissection
glycosylation
Hi-C
immunoprecipitation
ChIP-seq
electrophoretic mobility shift
ChIP
genotyping

Software Mentioned

PrediXcan
SMR
Hi
SNP effect matrix pipeline ( SEMpl )
MetaXcan
Moloc
Coloc

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