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

AUTHOR GROUP; Asa Johansson; Bernhard K. Kraemer; Braxton D. Mitchell; Brendan M. Buckley; Carmen A. Peralta; Caroline Hayward; Catherine Helmer; Charles N. Rotimi; Christian M. Shaffer; Christian Mueller; Cinzia Sala; Cornelia M. van Duijn; Aude Saint-Pierre; Daniel Ackermann; Daniel Shriner; Daniela Ruggiero; Daniela Toniolo; Yingchang Lu; Daniele Cusi; Darina Czamara; David Ellinghaus; David S. Siscovick; Douglas Ruderfer; Christian Gieger; Harald Grallert; Elena Rochtchina; Elizabeth J. Atkinson; Elizabeth G. Holliday; Eric Boerwinkle; Erika Salvi; Erwin P. Bottinger; Federico Murgia; Fernando Rivadeneira; Florian Ernst; Florian Kronenberg; Frank B. Hu; Gerjan J. Navis; Gary C. Curhan; George B. Ehret; Georg Homuth; Stefan Coassin; Gian-Andri Thun; Giorgio Pistis; Giovanni Gambaro; Giovanni Malerba; Grant W. Montgomery; Gudny Eiriksdottir; Gunnar Jacobs; Guo Li; H-Erich Wichmann; Harry Campbell; Helena Schmidt; Henri Wallaschofski; Henry Voelzke; Hermann Brenner; Heyo K. Kroemer; Holly Kramer; Honghuang Lin; I. Mateo Leach; Ian Ford; Idris Guessous; Igor Rudan; Inga Prokopenko; Ingrid Borecki; Iris M. Heid; Ivana Kolcic; Ivana Persico; J. Wouter Jukema; James F. Wilson; Janine F. Felix; Jasmin Divers; Jean-Charles Lambert; Jeanette M. Stafford; Jean-Michel Gaspoz; Jennifer A. Smith; Jessica D. Faul; Jie Jin Wang; Jingzhong Ding; Joel N. Hirschhorn; John Attia; John B. Whitfield; John Chalmers; Jorma Viikari; Josef Coresh; Joshua C. Denny; Juha Karjalainen; Jyotika K. Fernandes; Karlhans Endlich; Katja Butterbach; Keith L. Keene; Kurt Lohman; Laura Portas; Lenore J. Launer; Leo-Pekka Lyytikaeinen; Loic Yengo; Lude Franke; Luigi Ferrucci; Lynda M. Rose; Lyudmyla Kedenko; Madhumathi Rao; Maksim Struchalin; Marcus E. Kleber; Margherita Cavalieri; Margot Haun; Marilyn C. Cornelis; Marina Ciullo; Mario Pirastu; Mariza de Andrade; Mark A. McEvoy; Mark Woodward; Martin Adam; Massimiliano Cocca; Matthias Nauck; Medea Imboden; Melanie Waldenberger; Menno Pruijm; Marie Metzger; Michael Stumvoll; Michele K. Evans; Michele M. Sale; Mika Kaehoenen; Mladen Boban; Murielle Bochud; Myriam Rheinberger; Niek Verweij; Nabila Bouatia-Naji; Nicholas G. Martin; Nick Hastie; Nicole Probst-Hensch; Nicole Soranzo; Olivier Devuyst; Olli Raitakari; Omri Gottesman; Oscar H. Franco; Ozren Polasek; Paolo Gasparini; Patricia B. Munroe; Paul M. Ridker; Paul Mitchell; Paul Muntner; Christa Meisinger; Johannes H. Smit; Peter Kovacs; Philipp S. Wild; Philippe Froguel; Rainer Rettig; Reedik Maegi; Reiner Biffar; Reinhold Schmidt; Rita P. S. Middelberg; Robert J. Carroll; Brenda W. Penninx; Rodney J. Scott; Ronit Katz; Sanaz Sedaghat; Sarah H. Wild; Sharon L. R. Kardia; Sheila Ulivi; Shih-Jen Hwang; Stefan Enroth; Stefan Kloiber; Stella Trompet; Benedicte Stengel; Stephen J. Hancock; Stephen T. Turner; Sylvia E. Rosas; Sylvia Stracke; Tamara B. Harris; Tanja Zeller; Tatijana Zemunik; Terho Lehtimaeki; Thomas Illig; Thor Aspelund; Tiit Nikopensius; Tonu Esko; Toshiko Tanaka; Ulf Gyllensten; Uwe Voelker; Valur Emilsson; Veronique Vitart; Ville Aalto; Vilmundur Gudnason; Vincent Chouraki; Wei-Min Chen; Wilmar Igl; Winfried Maerz; Wolfgang Koenig; Wolfgang Lieb; Ruth J. F. Loos; Yongmei Liu; Harold Snieder; Peter P. Pramstaller; Afshin Parsa; Jeffrey R. O'Connell; Katalin Susztak; Pavel Hamet; Johanne Tremblay; Ian H. de Boer; Carsten A. Boeger; Wolfram Goessling; Daniel I. Chasman; Anna Koettgen; W. H. Linda Kao; Caroline S. Fox

doi:https://doi.org/10.1038/ncomms10023

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

AUTHOR GROUP, Asa Johansson, Bernhard K. Kraemer, Braxton D. Mitchell, Brendan M. Buckley, Carmen A. Peralta, Caroline Hayward, Catherine Helmer, Charles N. Rotimi, Christian M. Shaffer, Christian Mueller, Cinzia Sala, Cornelia M. van Duijn, Aude Saint-Pierre, Daniel Ackermann, Daniel Shriner, Daniela Ruggiero, Daniela Toniolo, Yingchang Lu, Daniele CusiDarina Czamara, David Ellinghaus, David S. Siscovick, Douglas Ruderfer, Christian Gieger, Harald Grallert, Elena Rochtchina, Elizabeth J. Atkinson, Elizabeth G. Holliday, Eric Boerwinkle, Erika Salvi, Erwin P. Bottinger, Federico Murgia, Fernando Rivadeneira, Florian Ernst, Florian Kronenberg, Frank B. Hu, Gerjan J. Navis, Gary C. Curhan, George B. Ehret, Georg Homuth, Stefan Coassin, Gian-Andri Thun, Giorgio Pistis, Giovanni Gambaro, Giovanni Malerba, Grant W. Montgomery, Gudny Eiriksdottir, Gunnar Jacobs, Guo Li, H-Erich Wichmann, Harry Campbell, Helena Schmidt, Henri Wallaschofski, Henry Voelzke, Hermann Brenner, Heyo K. Kroemer, Holly Kramer, Honghuang Lin, I. Mateo Leach, Ian Ford, Idris Guessous, Igor Rudan, Inga Prokopenko, Ingrid Borecki, Iris M. Heid, Ivana Kolcic, Ivana Persico, J. Wouter Jukema, James F. Wilson, Janine F. Felix, Jasmin Divers, Jean-Charles Lambert, Jeanette M. Stafford, Jean-Michel Gaspoz, Jennifer A. Smith, Jessica D. Faul, Jie Jin Wang, Jingzhong Ding, Joel N. Hirschhorn, John Attia, John B. Whitfield, John Chalmers, Jorma Viikari, Josef Coresh, Joshua C. Denny, Juha Karjalainen, Jyotika K. Fernandes, Karlhans Endlich, Katja Butterbach, Keith L. Keene, Kurt Lohman, Laura Portas, Lenore J. Launer, Leo-Pekka Lyytikaeinen, Loic Yengo, Lude Franke, Luigi Ferrucci, Lynda M. Rose, Lyudmyla Kedenko, Madhumathi Rao, Maksim Struchalin, Marcus E. Kleber, Margherita Cavalieri, Margot Haun, Marilyn C. Cornelis, Marina Ciullo, Mario Pirastu, Mariza de Andrade, Mark A. McEvoy, Mark Woodward, Martin Adam, Massimiliano Cocca, Matthias Nauck, Medea Imboden, Melanie Waldenberger, Menno Pruijm, Marie Metzger, Michael Stumvoll, Michele K. Evans, Michele M. Sale, Mika Kaehoenen, Mladen Boban, Murielle Bochud, Myriam Rheinberger, Niek Verweij, Nabila Bouatia-Naji, Nicholas G. Martin, Nick Hastie, Nicole Probst-Hensch, Nicole Soranzo, Olivier Devuyst, Olli Raitakari, Omri Gottesman, Oscar H. Franco, Ozren Polasek, Paolo Gasparini, Patricia B. Munroe, Paul M. Ridker, Paul Mitchell, Paul Muntner, Christa Meisinger, Johannes H. Smit, Peter Kovacs, Philipp S. Wild, Philippe Froguel, Rainer Rettig, Reedik Maegi, Reiner Biffar, Reinhold Schmidt, Rita P. S. Middelberg, Robert J. Carroll, Brenda W. Penninx, Rodney J. Scott, Ronit Katz, Sanaz Sedaghat, Sarah H. Wild, Sharon L. R. Kardia, Sheila Ulivi, Shih-Jen Hwang, Stefan Enroth, Stefan Kloiber, Stella Trompet, Benedicte Stengel, Stephen J. Hancock, Stephen T. Turner, Sylvia E. Rosas, Sylvia Stracke, Tamara B. Harris, Tanja Zeller, Tatijana Zemunik, Terho Lehtimaeki, Thomas Illig, Thor Aspelund, Tiit Nikopensius, Tonu Esko, Toshiko Tanaka, Ulf Gyllensten, Uwe Voelker, Valur Emilsson, Veronique Vitart, Ville Aalto, Vilmundur Gudnason, Vincent Chouraki, Wei-Min Chen, Wilmar Igl, Winfried Maerz, Wolfgang Koenig, Wolfgang Lieb, Ruth J. F. Loos, Yongmei Liu, Harold Snieder, Peter P. Pramstaller, Afshin Parsa, Jeffrey R. O'Connell, Katalin Susztak, Pavel Hamet, Johanne Tremblay, Ian H. de Boer, Carsten A. Boeger, Wolfram Goessling, Daniel I. Chasman, Anna Koettgen, W. H. Linda Kao, Caroline S. Fox

Psychiatry (VUmc)

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

337 Citations (Scopus)

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
Pages (from-to)	10023
Journal	Nature communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms10023
Publication status	Published - Jan 2016

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https://doi.org/10.1038/ncomms10023

Cite this

AUTHOR GROUP, Johansson, A., Kraemer, B. K., Mitchell, B. D., Buckley, B. M., Peralta, C. A., Hayward, C., Helmer, C., Rotimi, C. N., Shaffer, C. M., Mueller, C., Sala, C., van Duijn, C. M., Saint-Pierre, A., Ackermann, D., Shriner, D., Ruggiero, D., Toniolo, D., Lu, Y., ... Fox, C. S. (2016). Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function. Nature communications, 7, 10023. https://doi.org/10.1038/ncomms10023

@article{cb31974c3ca940159f7da569a7a6e081,

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",

author = "{AUTHOR GROUP} and 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 {\AA}sa Johansson and Ayse Demirkan and Barbara Kollerits and Freedman, {Barry I.} and Belen Ponte and Oostra, {Ben A.} and Bernhard Paulweber and Kr{\"a}mer, {Bernhard K.} and Asa Johansson and Kraemer, {Bernhard K.} and Mitchell, {Braxton D.} and Buckley, {Brendan M.} and Peralta, {Carmen A.} and Caroline Hayward and Catherine Helmer and Rotimi, {Charles N.} and Shaffer, {Christian M.} and Christian Mueller and Cinzia Sala and {van Duijn}, {Cornelia M.} and Aude Saint-Pierre and Daniel Ackermann and Daniel Shriner and Daniela Ruggiero and Daniela Toniolo and Yingchang Lu and Daniele Cusi and Darina Czamara and David Ellinghaus and Siscovick, {David S.} and Douglas Ruderfer and Christian Gieger and Harald Grallert and Elena Rochtchina and Atkinson, {Elizabeth J.} and Holliday, {Elizabeth G.} and Eric Boerwinkle and Erika Salvi and Bottinger, {Erwin P.} and Federico Murgia and Fernando Rivadeneira and Florian Ernst and Florian Kronenberg and Hu, {Frank B.} and Navis, {Gerjan J.} and Curhan, {Gary C.} and Ehret, {George B.} and Georg Homuth and Stefan Coassin and Gian-Andri Thun and Giorgio Pistis and Giovanni Gambaro and Giovanni Malerba and Montgomery, {Grant W.} and Gudny Eiriksdottir and Gunnar Jacobs and Guo Li and H-Erich Wichmann and Harry Campbell and Helena Schmidt and Henri Wallaschofski and Henry Voelzke and Hermann Brenner and Kroemer, {Heyo K.} and Holly Kramer and Honghuang Lin and Leach, {I. Mateo} and Ian Ford and Idris Guessous and Igor Rudan and Inga Prokopenko and Ingrid Borecki and Heid, {Iris M.} and Ivana Kolcic and Ivana Persico and Jukema, {J. Wouter} and Wilson, {James F.} and Felix, {Janine F.} and Jasmin Divers and Jean-Charles Lambert and Stafford, {Jeanette M.} and Jean-Michel Gaspoz and Smith, {Jennifer A.} and Faul, {Jessica D.} and Wang, {Jie Jin} and Jingzhong Ding and Hirschhorn, {Joel N.} and John Attia and Whitfield, {John B.} and John Chalmers and Jorma Viikari and Josef Coresh and Denny, {Joshua C.} and Juha Karjalainen and Fernandes, {Jyotika K.} and Karlhans Endlich and Katja Butterbach and Keene, {Keith L.} and Kurt Lohman and Laura Portas and Launer, {Lenore J.} and Leo-Pekka Lyytikaeinen and Loic Yengo and Lude Franke and Luigi Ferrucci and Rose, {Lynda M.} and Lyudmyla Kedenko and Madhumathi Rao and Maksim Struchalin and Kleber, {Marcus E.} and Margherita Cavalieri and Margot Haun and Cornelis, {Marilyn C.} and Marina Ciullo and Mario Pirastu and {de Andrade}, Mariza and McEvoy, {Mark A.} and Mark Woodward and Martin Adam and Massimiliano Cocca and Matthias Nauck and Medea Imboden and Melanie Waldenberger and Menno Pruijm and Marie Metzger and Michael Stumvoll and Evans, {Michele K.} and Sale, {Michele M.} and Mika Kaehoenen and Mladen Boban and Murielle Bochud and Myriam Rheinberger and Niek Verweij and Nabila Bouatia-Naji and Martin, {Nicholas G.} and Nick Hastie and Nicole Probst-Hensch and Nicole Soranzo and Olivier Devuyst and Olli Raitakari and Omri Gottesman and Franco, {Oscar H.} and Ozren Polasek and Paolo Gasparini and Munroe, {Patricia B.} and Ridker, {Paul M.} and Paul Mitchell and Paul Muntner and Christa Meisinger and Smit, {Johannes H.} and Peter Kovacs and Wild, {Philipp S.} and Philippe Froguel and Rainer Rettig and Reedik Maegi and Reiner Biffar and Reinhold Schmidt and Middelberg, {Rita P. S.} and Carroll, {Robert J.} and Penninx, {Brenda W.} and Scott, {Rodney J.} and Ronit Katz and Sanaz Sedaghat and Wild, {Sarah H.} and Kardia, {Sharon L. R.} and Sheila Ulivi and Shih-Jen Hwang and Stefan Enroth and Stefan Kloiber and Stella Trompet and Benedicte Stengel and Hancock, {Stephen J.} and Turner, {Stephen T.} and Rosas, {Sylvia E.} and Sylvia Stracke and Harris, {Tamara B.} and Tanja Zeller and Tatijana Zemunik and Terho Lehtimaeki and Thomas Illig and Thor Aspelund and Tiit Nikopensius and Tonu Esko and Toshiko Tanaka and Ulf Gyllensten and Uwe Voelker and Valur Emilsson and Veronique Vitart and Ville Aalto and Vilmundur Gudnason and Vincent Chouraki and Wei-Min Chen and Wilmar Igl and Winfried Maerz and Wolfgang Koenig and Wolfgang Lieb and Loos, {Ruth J. F.} and Yongmei Liu and Harold Snieder and Pramstaller, {Peter P.} and Afshin Parsa and O'Connell, {Jeffrey R.} and Katalin Susztak and Pavel Hamet and Johanne Tremblay and {de Boer}, {Ian H.} and Boeger, {Carsten A.} and Wolfram Goessling and Chasman, {Daniel I.} and Anna Koettgen and Kao, {W. H. Linda} and Fox, {Caroline S.}",

year = "2016",

month = jan,

doi = "https://doi.org/10.1038/ncomms10023",

language = "English",

volume = "7",

pages = "10023",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

AUTHOR GROUP, Johansson, A, Kraemer, BK, Mitchell, BD, Buckley, BM, Peralta, CA, Hayward, C, Helmer, C, Rotimi, CN, Shaffer, CM, Mueller, C, Sala, C, van Duijn, CM, Saint-Pierre, A, Ackermann, D, Shriner, D, Ruggiero, D, Toniolo, D, Lu, Y, Cusi, D, Czamara, D, Ellinghaus, D, Siscovick, DS, Ruderfer, D, Gieger, C, Grallert, H, Rochtchina, E, Atkinson, EJ, Holliday, EG, Boerwinkle, E, Salvi, E, Bottinger, EP, Murgia, F, Rivadeneira, F, Ernst, F, Kronenberg, F, Hu, FB, Navis, GJ, Curhan, GC, Ehret, GB, Homuth, G, Coassin, S, Thun, G-A, Pistis, G, Gambaro, G, Malerba, G, Montgomery, GW, Eiriksdottir, G, Jacobs, G, Li, G, Wichmann, H-E, Campbell, H, Schmidt, H, Wallaschofski, H, Voelzke, H, Brenner, H, Kroemer, HK, Kramer, H, Lin, H, Leach, IM, Ford, I, Guessous, I, Rudan, I, Prokopenko, I, Borecki, I, Heid, IM, Kolcic, I, Persico, I, Jukema, JW, Wilson, JF, Felix, JF, Divers, J, Lambert, J-C, Stafford, JM, Gaspoz, J-M, Smith, JA, Faul, JD, Wang, JJ, Ding, J, Hirschhorn, JN, Attia, J, Whitfield, JB, Chalmers, J, Viikari, J, Coresh, J, Denny, JC, Karjalainen, J, Fernandes, JK, Endlich, K, Butterbach, K, Keene, KL, Lohman, K, Portas, L, Launer, LJ, Lyytikaeinen, L-P, Yengo, L, Franke, L, Ferrucci, L, Rose, LM, Kedenko, L, Rao, M, Struchalin, M, Kleber, ME, Cavalieri, M, Haun, M, Cornelis, MC, Ciullo, M, Pirastu, M, de Andrade, M, McEvoy, MA, Woodward, M, Adam, M, Cocca, M, Nauck, M, Imboden, M, Waldenberger, M, Pruijm, M, Metzger, M, Stumvoll, M, Evans, MK, Sale, MM, Kaehoenen, M, Boban, M, Bochud, M, Rheinberger, M, Verweij, N, Bouatia-Naji, N, Martin, NG, Hastie, N, Probst-Hensch, N, Soranzo, N, Devuyst, O, Raitakari, O, Gottesman, O, Franco, OH, Polasek, O, Gasparini, P, Munroe, PB, Ridker, PM, Mitchell, P, Muntner, P, Meisinger, C, Smit, JH, Kovacs, P, Wild, PS, Froguel, P, Rettig, R, Maegi, R, Biffar, R, Schmidt, R, Middelberg, RPS, Carroll, RJ, Penninx, BW, Scott, RJ, Katz, R, Sedaghat, S, Wild, SH, Kardia, SLR, Ulivi, S, Hwang, S-J, Enroth, S, Kloiber, S, Trompet, S, Stengel, B, Hancock, SJ, Turner, ST, Rosas, SE, Stracke, S, Harris, TB, Zeller, T, Zemunik, T, Lehtimaeki, T, Illig, T, Aspelund, T, Nikopensius, T, Esko, T, Tanaka, T, Gyllensten, U, Voelker, U, Emilsson, V, Vitart, V, Aalto, V, Gudnason, V, Chouraki, V, Chen, W-M, Igl, W, Maerz, W, Koenig, W, Lieb, W, Loos, RJF, Liu, Y, Snieder, H, Pramstaller, PP, Parsa, A, O'Connell, JR, Susztak, K, Hamet, P, Tremblay, J, de Boer, IH, Boeger, CA, Goessling, W, Chasman, DI, Koettgen, A, Kao, WHL & Fox, CS 2016, 'Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function', Nature communications, vol. 7, pp. 10023. 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 - AUTHOR GROUP

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, Åsa

AU - Demirkan, Ayse

AU - Kollerits, Barbara

AU - Freedman, Barry I.

AU - Ponte, Belen

AU - Oostra, Ben A.

AU - Paulweber, Bernhard

AU - Krämer, Bernhard K.

AU - Johansson, Asa

AU - Kraemer, Bernhard K.

AU - Mitchell, Braxton D.

AU - Buckley, Brendan M.

AU - Peralta, Carmen A.

AU - Hayward, Caroline

AU - Helmer, Catherine

AU - Rotimi, Charles N.

AU - Shaffer, Christian M.

AU - Mueller, Christian

AU - Sala, Cinzia

AU - van Duijn, Cornelia M.

AU - Saint-Pierre, Aude

AU - Ackermann, Daniel

AU - Shriner, Daniel

AU - Ruggiero, Daniela

AU - Toniolo, Daniela

AU - Lu, Yingchang

AU - Cusi, Daniele

AU - Czamara, Darina

AU - Ellinghaus, David

AU - Siscovick, David S.

AU - Ruderfer, Douglas

AU - Gieger, Christian

AU - Grallert, Harald

AU - Rochtchina, Elena

AU - Atkinson, Elizabeth J.

AU - Holliday, Elizabeth G.

AU - Boerwinkle, Eric

AU - Salvi, Erika

AU - Bottinger, Erwin P.

AU - Murgia, Federico

AU - Rivadeneira, Fernando

AU - Ernst, Florian

AU - Kronenberg, Florian

AU - Hu, Frank B.

AU - Navis, Gerjan J.

AU - Curhan, Gary C.

AU - Ehret, George B.

AU - Homuth, Georg

AU - Coassin, Stefan

AU - Thun, Gian-Andri

AU - Pistis, Giorgio

AU - Gambaro, Giovanni

AU - Malerba, Giovanni

AU - Montgomery, Grant W.

AU - Eiriksdottir, Gudny

AU - Jacobs, Gunnar

AU - Li, Guo

AU - Wichmann, H-Erich

AU - Campbell, Harry

AU - Schmidt, Helena

AU - Wallaschofski, Henri

AU - Voelzke, Henry

AU - Brenner, Hermann

AU - Kroemer, Heyo K.

AU - Kramer, Holly

AU - Lin, Honghuang

AU - Leach, I. Mateo

AU - Ford, Ian

AU - Guessous, Idris

AU - Rudan, Igor

AU - Prokopenko, Inga

AU - Borecki, Ingrid

AU - Heid, Iris M.

AU - Kolcic, Ivana

AU - Persico, Ivana

AU - Jukema, J. Wouter

AU - Wilson, James F.

AU - Felix, Janine F.

AU - Divers, Jasmin

AU - Lambert, Jean-Charles

AU - Stafford, Jeanette M.

AU - Gaspoz, Jean-Michel

AU - Smith, Jennifer A.

AU - Faul, Jessica D.

AU - Wang, Jie Jin

AU - Ding, Jingzhong

AU - Hirschhorn, Joel N.

AU - Attia, John

AU - Whitfield, John B.

AU - Chalmers, John

AU - Viikari, Jorma

AU - Coresh, Josef

AU - Denny, Joshua C.

AU - Karjalainen, Juha

AU - Fernandes, Jyotika K.

AU - Endlich, Karlhans

AU - Butterbach, Katja

AU - Keene, Keith L.

AU - Lohman, Kurt

AU - Portas, Laura

AU - Launer, Lenore J.

AU - Lyytikaeinen, Leo-Pekka

AU - Yengo, Loic

AU - Franke, Lude

AU - Ferrucci, Luigi

AU - Rose, Lynda M.

AU - Kedenko, Lyudmyla

AU - Rao, Madhumathi

AU - Struchalin, Maksim

AU - Kleber, Marcus E.

AU - Cavalieri, Margherita

AU - Haun, Margot

AU - Cornelis, Marilyn C.

AU - Ciullo, Marina

AU - Pirastu, Mario

AU - de Andrade, Mariza

AU - McEvoy, Mark A.

AU - Woodward, Mark

AU - Adam, Martin

AU - Cocca, Massimiliano

AU - Nauck, Matthias

AU - Imboden, Medea

AU - Waldenberger, Melanie

AU - Pruijm, Menno

AU - Metzger, Marie

AU - Stumvoll, Michael

AU - Evans, Michele K.

AU - Sale, Michele M.

AU - Kaehoenen, Mika

AU - Boban, Mladen

AU - Bochud, Murielle

AU - Rheinberger, Myriam

AU - Verweij, Niek

AU - Bouatia-Naji, Nabila

AU - Martin, Nicholas G.

AU - Hastie, Nick

AU - Probst-Hensch, Nicole

AU - Soranzo, Nicole

AU - Devuyst, Olivier

AU - Raitakari, Olli

AU - Gottesman, Omri

AU - Franco, Oscar H.

AU - Polasek, Ozren

AU - Gasparini, Paolo

AU - Munroe, Patricia B.

AU - Ridker, Paul M.

AU - Mitchell, Paul

AU - Muntner, Paul

AU - Meisinger, Christa

AU - Smit, Johannes H.

AU - Kovacs, Peter

AU - Wild, Philipp S.

AU - Froguel, Philippe

AU - Rettig, Rainer

AU - Maegi, Reedik

AU - Biffar, Reiner

AU - Schmidt, Reinhold

AU - Middelberg, Rita P. S.

AU - Carroll, Robert J.

AU - Penninx, Brenda W.

AU - Scott, Rodney J.

AU - Katz, Ronit

AU - Sedaghat, Sanaz

AU - Wild, Sarah H.

AU - Kardia, Sharon L. R.

AU - Ulivi, Sheila

AU - Hwang, Shih-Jen

AU - Enroth, Stefan

AU - Kloiber, Stefan

AU - Trompet, Stella

AU - Stengel, Benedicte

AU - Hancock, Stephen J.

AU - Turner, Stephen T.

AU - Rosas, Sylvia E.

AU - Stracke, Sylvia

AU - Harris, Tamara B.

AU - Zeller, Tanja

AU - Zemunik, Tatijana

AU - Lehtimaeki, Terho

AU - Illig, Thomas

AU - Aspelund, Thor

AU - Nikopensius, Tiit

AU - Esko, Tonu

AU - Tanaka, Toshiko

AU - Gyllensten, Ulf

AU - Voelker, Uwe

AU - Emilsson, Valur

AU - Vitart, Veronique

AU - Aalto, Ville

AU - Gudnason, Vilmundur

AU - Chouraki, Vincent

AU - Chen, Wei-Min

AU - Igl, Wilmar

AU - Maerz, Winfried

AU - Koenig, Wolfgang

AU - Lieb, Wolfgang

AU - Loos, Ruth J. F.

AU - Liu, Yongmei

AU - Snieder, Harold

AU - Pramstaller, Peter P.

AU - Parsa, Afshin

AU - O'Connell, Jeffrey R.

AU - Susztak, Katalin

AU - Hamet, Pavel

AU - Tremblay, Johanne

AU - de Boer, Ian H.

AU - Boeger, Carsten A.

AU - Goessling, Wolfram

AU - Chasman, Daniel I.

AU - Koettgen, Anna

AU - Kao, W. H. Linda

AU - Fox, Caroline S.

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

U2 - https://doi.org/10.1038/ncomms10023

DO - https://doi.org/10.1038/ncomms10023

M3 - Article

C2 - 26831199

SN - 2041-1723

VL - 7

SP - 10023

JO - Nature communications

JF - Nature communications

ER -