Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
C., Pattaro ; Fava, C. LU ; Hedblad, B. LU ; Melander, O. LU
; Nilsson, P.
LU
; Sjögren, M.
LU
and C.S., Fox
(2016)
In Nature Communications
7.
- Abstract
- Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and... (More)
- Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/cf4d2963-8fdc-45d0-a3ec-1c894cb0f1a4
- author
- C., Pattaro
; Fava, C.
LU
; Hedblad, B.
LU
; Melander, O.
LU
; Nilsson, P.
LU
; Sjögren, M.
LU
and C.S., Fox
- author collaboration
- organization
- publishing date
- 2016
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- biological marker, creatinine, cystatin C, deoxyribonuclease I, morpholino oligonucleotide, cardiovascular disease, cells and cell components, diabetes, enzyme activity, genetic analysis, glucose, meta-analysis, metabolism, physiological response, adrenal cortex, adrenal gland, adult, Article, bioinformatics, chromatin, controlled study, creatinine blood level, diabetes mellitus, embryo, embryonic stem cell, ethnic group, ethnicity, gene locus, gene replication, genetic association, genetic susceptibility, genetic variability, genotype, glomerulus filtration rate, glucose metabolism, human, human cell, hypertension, kidney cell, kidney development, kidney epithelium, kidney function, kidney parenchyma, kidney proximal tubule, kidney structure, phenotype, single nucleotide polymorphism, chronic kidney failure, gene expression regulation, genetic predisposition, genetics, genome-wide association study, meta analysis, Gene Expression Regulation, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Renal Insufficiency, Chronic
- in
- Nature Communications
- volume
- 7
- article number
- 10023
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:84957605211
- ISSN
- 2041-1723
- DOI
- 10.1038/ncomms10023
- language
- English
- LU publication?
- yes
- id
- cf4d2963-8fdc-45d0-a3ec-1c894cb0f1a4
- date added to LUP
- 2022-04-04 13:38:01
- date last changed
- 2024-01-06 13:21:07
@article{cf4d2963-8fdc-45d0-a3ec-1c894cb0f1a4,
abstract = {{Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.}},
author = {{C., Pattaro and Fava, C. and Hedblad, B. and Melander, O. and Nilsson, P. and Sjögren, M. and C.S., Fox}},
issn = {{2041-1723}},
keywords = {{biological marker; creatinine; cystatin C; deoxyribonuclease I; morpholino oligonucleotide; cardiovascular disease; cells and cell components; diabetes; enzyme activity; genetic analysis; glucose; meta-analysis; metabolism; physiological response; adrenal cortex; adrenal gland; adult; Article; bioinformatics; chromatin; controlled study; creatinine blood level; diabetes mellitus; embryo; embryonic stem cell; ethnic group; ethnicity; gene locus; gene replication; genetic association; genetic susceptibility; genetic variability; genotype; glomerulus filtration rate; glucose metabolism; human; human cell; hypertension; kidney cell; kidney development; kidney epithelium; kidney function; kidney parenchyma; kidney proximal tubule; kidney structure; phenotype; single nucleotide polymorphism; chronic kidney failure; gene expression regulation; genetic predisposition; genetics; genome-wide association study; meta analysis; Gene Expression Regulation; Genetic Predisposition to Disease; Genome-Wide Association Study; Genotype; Humans; Renal Insufficiency, Chronic}},
language = {{eng}},
publisher = {{Nature Publishing Group}},
series = {{Nature Communications}},
title = {{Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function}},
url = {{http://dx.doi.org/10.1038/ncomms10023}},
doi = {{10.1038/ncomms10023}},
volume = {{7}},
year = {{2016}},
}