Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function

Cristian Pattaro; Alexander Teumer; Mathias Gorski; Audrey Y. Chu; Man Li; Vladan Mijatovic; Maija Garnaas; Adrienne Tin; Rossella Sorice; Yong Li; Daniel Taliun; Matthias Olden; Meredith Foster; Qiong Yang; Ming-Huei Chen; Tune H. Pers; Andrew D. Johnson; Yi-An Ko; Christian Fuchsberger; Bamidele Tayo; Michael Nalls; Mary F. Feitosa; Aaron Isaacs; Abbas Dehghan; Pio d'Adamo; Adebowale Adeyemo; Aida Karina Dieffenbach; Alan B. Zonderman; Ilja M. Nolte; Peter J. van der Most; Alan F. Wright; Alan R. Shuldiner; Alanna C. Morrison; Albert Hofman; Albert V. Smith; Albert W. Dreisbach; Andre Franke; Andre G. Uitterlinden; Andres Metspalu; Anke Tonjes; Antonio Lupo; Antonietta Robino; Asa Johansson; Ayse Demirkan; Barbara Kollerits; Barry I. Freedman; Belen Ponte; Ben A. Oostra; Bernhard Paulweber; Bernhard K. Kraemer; Author collaboration

doi:10.1038/ncomms10023

Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function

Cristian Pattaro^*, Alexander Teumer, Mathias Gorski, Audrey Y. Chu, Man Li, Vladan Mijatovic, Maija Garnaas, Adrienne Tin, Rossella Sorice, Yong Li, Daniel Taliun, Matthias Olden, Meredith Foster, Qiong Yang, Ming-Huei Chen, Tune H. Pers, Andrew D. Johnson, Yi-An Ko, Christian Fuchsberger, Bamidele TayoMichael Nalls, Mary F. Feitosa, Aaron Isaacs, Abbas Dehghan, Pio d'Adamo, Adebowale Adeyemo, Aida Karina Dieffenbach, Alan B. Zonderman, Ilja M. Nolte, Peter J. van der Most, Alan F. Wright, Alan R. Shuldiner, Alanna C. Morrison, Albert Hofman, Albert V. Smith, Albert W. Dreisbach, Andre Franke, Andre G. Uitterlinden, Andres Metspalu, Anke Tonjes, Antonio Lupo, Antonietta Robino, Asa Johansson, Ayse Demirkan, Barbara Kollerits, Barry I. Freedman, Belen Ponte, Ben A. Oostra, Bernhard Paulweber, Bernhard K. Kraemer, Author collaboration

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Number of pages	19
Journal	Nature Communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms10023
Publication status	Published - Jan 2016

Keywords

Genome-wide association
Stage renal-disease
Serum creatinine
Metaanalysis
Individuals
Hypertension
Replication
Environment
Mortality
Efficient

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10.1038/ncomms10023Licence: CC BY

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Pattaro, C., Teumer, A., Gorski, M., Chu, A. Y., Li, M., Mijatovic, V., Garnaas, M., Tin, A., Sorice, R., Li, Y., Taliun, D., Olden, M., Foster, M., Yang, Q., Chen, M.-H., Pers, T. H., Johnson, A. D., Ko, Y.-A., Fuchsberger, C., ... Author collaboration (2016). Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function. Nature Communications, 7. https://doi.org/10.1038/ncomms10023

@article{b266452ac40e42858a9da22200d55872,

title = "Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function",

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.",

keywords = "Genome-wide association, Stage renal-disease, Serum creatinine, Metaanalysis, Individuals, Hypertension, Replication, Environment, Mortality, Efficient",

author = "Cristian Pattaro and Alexander Teumer and Mathias Gorski and Chu, {Audrey Y.} and Man Li and Vladan Mijatovic and Maija Garnaas and Adrienne Tin and Rossella Sorice and Yong Li and Daniel Taliun and Matthias Olden and Meredith Foster and Qiong Yang and Ming-Huei Chen and Pers, {Tune H.} and Johnson, {Andrew D.} and Yi-An Ko and Christian Fuchsberger and Bamidele Tayo and Michael Nalls and Feitosa, {Mary F.} and Aaron Isaacs and Abbas Dehghan and Pio d'Adamo and Adebowale Adeyemo and Dieffenbach, {Aida Karina} and Zonderman, {Alan B.} and Nolte, {Ilja M.} and {van der Most}, {Peter J.} and Wright, {Alan F.} and Shuldiner, {Alan R.} and Morrison, {Alanna C.} and Albert Hofman and Smith, {Albert V.} and Dreisbach, {Albert W.} and Andre Franke and Uitterlinden, {Andre G.} and Andres Metspalu and Anke Tonjes and Antonio Lupo and Antonietta Robino and Asa Johansson and Ayse Demirkan and Barbara Kollerits and Freedman, {Barry I.} and Belen Ponte and Oostra, {Ben A.} and Bernhard Paulweber and Kraemer, {Bernhard K.} and {Author collaboration}",

year = "2016",

month = jan,

doi = "10.1038/ncomms10023",

language = "English",

volume = "7",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

Pattaro, C, Teumer, A, Gorski, M, Chu, AY, Li, M, Mijatovic, V, Garnaas, M, Tin, A, Sorice, R, Li, Y, Taliun, D, Olden, M, Foster, M, Yang, Q, Chen, M-H, Pers, TH, Johnson, AD, Ko, Y-A, Fuchsberger, C, Tayo, B, Nalls, M, Feitosa, MF, Isaacs, A, Dehghan, A, d'Adamo, P, Adeyemo, A, Dieffenbach, AK, Zonderman, AB, Nolte, IM, van der Most, PJ, Wright, AF, Shuldiner, AR, Morrison, AC, Hofman, A, Smith, AV, Dreisbach, AW, Franke, A, Uitterlinden, AG, Metspalu, A, Tonjes, A, Lupo, A, Robino, A, Johansson, A, Demirkan, A, Kollerits, B, Freedman, BI, Ponte, B, Oostra, BA, Paulweber, B, Kraemer, BK & Author collaboration 2016, 'Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function', Nature Communications, vol. 7. https://doi.org/10.1038/ncomms10023

TY - JOUR

T1 - Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function

AU - Pattaro, Cristian

AU - Teumer, Alexander

AU - Gorski, Mathias

AU - Chu, Audrey Y.

AU - Li, Man

AU - Mijatovic, Vladan

AU - Garnaas, Maija

AU - Tin, Adrienne

AU - Sorice, Rossella

AU - Li, Yong

AU - Taliun, Daniel

AU - Olden, Matthias

AU - Foster, Meredith

AU - Yang, Qiong

AU - Chen, Ming-Huei

AU - Pers, Tune H.

AU - Johnson, Andrew D.

AU - Ko, Yi-An

AU - Fuchsberger, Christian

AU - Tayo, Bamidele

AU - Nalls, Michael

AU - Feitosa, Mary F.

AU - Isaacs, Aaron

AU - Dehghan, Abbas

AU - d'Adamo, Pio

AU - Adeyemo, Adebowale

AU - Dieffenbach, Aida Karina

AU - Zonderman, Alan B.

AU - Nolte, Ilja M.

AU - van der Most, Peter J.

AU - Wright, Alan F.

AU - Shuldiner, Alan R.

AU - Morrison, Alanna C.

AU - Hofman, Albert

AU - Smith, Albert V.

AU - Dreisbach, Albert W.

AU - Franke, Andre

AU - Uitterlinden, Andre G.

AU - Metspalu, Andres

AU - Tonjes, Anke

AU - Lupo, Antonio

AU - Robino, Antonietta

AU - Johansson, Asa

AU - Demirkan, Ayse

AU - Kollerits, Barbara

AU - Freedman, Barry I.

AU - Ponte, Belen

AU - Oostra, Ben A.

AU - Paulweber, Bernhard

AU - Kraemer, Bernhard K.

AU - Author collaboration

PY - 2016/1

Y1 - 2016/1

N2 - 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.

AB - 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.

KW - Genome-wide association

KW - Stage renal-disease

KW - Serum creatinine

KW - Metaanalysis

KW - Individuals

KW - Hypertension

KW - Replication

KW - Environment

KW - Mortality

KW - Efficient

U2 - 10.1038/ncomms10023

DO - 10.1038/ncomms10023

M3 - Article

C2 - 26831199

SN - 2041-1723

VL - 7

JO - Nature Communications

JF - Nature Communications

ER -

Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function

Abstract

Keywords

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