Genome-wide association and functional follow-up reveals new loci for kidney function

Cristian Pattaro, Anna Köttgen, Alexander Teumer, Maija Garnaas, Carsten A. Böger, Christian Fuchsberger, Matthias Olden, Ming Huei Chen, Adrienne Tin, Daniel Taliun, Man Li, Xiaoyi Gao, Mathias Gorski, Qiong Yang, Claudia Hundertmark, Meredith C. Foster, Conall M. O'Seaghdha, Nicole Glazer, Aaron Isaacs, Ching Ti Liu & 146 others Albert V. Smith, Jeffrey R. O'Connell, Maksim Struchalin, Toshiko Tanaka, Guo Li, Andrew D. Johnson, Hinco J. Gierman, Mary Feitosa, Shih Jen Hwang, Elizabeth J. Atkinson, Kurt Lohman, Marilyn C. Cornelis, Åsa Johansson, Anke Tönjes, Abbas Dehghan, Vincent Chouraki, Elizabeth G. Holliday, Rossella Sorice, Zoltan Kutalik, Terho Lehtimäki, Tõnu Esko, Harshal Deshmukh, Sheila Ulivi, Audrey Y. Chu, Federico Murgia, Stella Trompet, Medea Imboden, Barbara Kollerits, Giorgio Pistis, Tamara B. Harris, Lenore J. Launer, Thor Aspelund, Gudny Eiriksdottir, Braxton D. Mitchell, Eric Boerwinkle, Helena Schmidt, Margherita Cavalieri, Madhumathi Rao, Frank B. Hu, Ayse Demirkan, Ben A. Oostra, Mariza de Andrade, Stephen T. Turner, Jingzhong Ding, Jeanette S. Andrews, Barry I. Freedman, Wolfgang Koenig, Thomas Illig, Angela Döring, H. Erich Wichmann, Ivana Kolcic, Tatijana Zemunik, Mladen Boban, Cosetta Minelli, Heather E. Wheeler, Wilmar Igl, Ghazal Zaboli, Sarah H. Wild, Alan F. Wright, Harry Campbell, David Ellinghaus, Ute Nöthlings, Gunnar Jacobs, Reiner Biffar, Karlhans Endlich, Florian Ernst, Georg Homuth, Heyo K. Kroemer, Matthias Nauck, Sylvia Stracke, Uwe Völker, Henry Völzke, Peter Kovacs, Michael Stumvoll, Reedik Mägi, Albert Hofman, Andre G. Uitterlinden, Fernando Rivadeneira, Yurii S. Aulchenko, Ozren Polasek, Nick Hastie, Veronique Vitart, Catherine Helmer, Jie Jin Wang, Daniela Ruggiero, Sven Bergmann, Mika Kähönen, Jorma Viikari, Tiit Nikopensius, Michael Province, Shamika Ketkar, Helen Colhoun, Alex Doney, Antonietta Robino, Franco Giulianini, Bernhard K. Krämer, Laura Portas, Ian Ford, Brendan M. Buckley, Martin Adam, Gian Andri Thun, Bernhard Paulweber, Margot Haun, Cinzia Sala, Marie Metzger, Paul Mitchell, Marina Ciullo, Stuart K. Kim, Peter Vollenweider, Olli Raitakari, Andres Metspalu, Colin Palmer, Paolo Gasparini, Mario Pirastu, J. Wouter Jukema, Nicole M. Probst-Hensch, Florian Kronenberg, Daniela Toniolo, Vilmundur Gudnason, Alan R. Shuldiner, Josef Coresh, Reinhold Schmidt, Luigi Ferrucci, David S. Siscovick, Cornelia M. van Duijn, Ingrid Borecki, Sharon L R Kardia, Yongmei Liu, Gary C. Curhan, Igor Rudan, Ulf Gyllensten, James F. Wilson, Andre Franke, Peter P. Pramstaller, Rainer Rettig, Inga Prokopenko, Jacqueline C M Witteman, Caroline Hayward, Paul Ridker, Afshin Parsa, Murielle Bochud, Iris M. Heid, Wolfram Goessling, Daniel I. Chasman, W. H Linda Kao, Caroline S. Fox

Research output: Contribution to journalArticle

Abstract

Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genome-wide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD.

Original languageEnglish (US)
Article numbere1002584
JournalPLoS Genetics
Volume8
Issue number3
DOIs
StatePublished - Mar 2012

Fingerprint

renal function
kidney diseases
Chronic Renal Insufficiency
genome
Genome
Kidney
loci
Morpholinos
Podocytes
glomerular filtration rate
gene
Genome-Wide Association Study
dextran
Zebrafish
abnormality
Dextrans
Glomerular Filtration Rate
Danio rerio
risk factor
ancestry

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)

Cite this

Pattaro, C., Köttgen, A., Teumer, A., Garnaas, M., Böger, C. A., Fuchsberger, C., ... Fox, C. S. (2012). Genome-wide association and functional follow-up reveals new loci for kidney function. PLoS Genetics, 8(3), [e1002584]. https://doi.org/10.1371/journal.pgen.1002584

Genome-wide association and functional follow-up reveals new loci for kidney function. / Pattaro, Cristian; Köttgen, Anna; Teumer, Alexander; Garnaas, Maija; Böger, Carsten A.; Fuchsberger, Christian; Olden, Matthias; Chen, Ming Huei; Tin, Adrienne; Taliun, Daniel; Li, Man; Gao, Xiaoyi; Gorski, Mathias; Yang, Qiong; Hundertmark, Claudia; Foster, Meredith C.; O'Seaghdha, Conall M.; Glazer, Nicole; Isaacs, Aaron; Liu, Ching Ti; Smith, Albert V.; O'Connell, Jeffrey R.; Struchalin, Maksim; Tanaka, Toshiko; Li, Guo; Johnson, Andrew D.; Gierman, Hinco J.; Feitosa, Mary; Hwang, Shih Jen; Atkinson, Elizabeth J.; Lohman, Kurt; Cornelis, Marilyn C.; Johansson, Åsa; Tönjes, Anke; Dehghan, Abbas; Chouraki, Vincent; Holliday, Elizabeth G.; Sorice, Rossella; Kutalik, Zoltan; Lehtimäki, Terho; Esko, Tõnu; Deshmukh, Harshal; Ulivi, Sheila; Chu, Audrey Y.; Murgia, Federico; Trompet, Stella; Imboden, Medea; Kollerits, Barbara; Pistis, Giorgio; Harris, Tamara B.; Launer, Lenore J.; Aspelund, Thor; Eiriksdottir, Gudny; Mitchell, Braxton D.; Boerwinkle, Eric; Schmidt, Helena; Cavalieri, Margherita; Rao, Madhumathi; Hu, Frank B.; Demirkan, Ayse; Oostra, Ben A.; de Andrade, Mariza; Turner, Stephen T.; Ding, Jingzhong; Andrews, Jeanette S.; Freedman, Barry I.; Koenig, Wolfgang; Illig, Thomas; Döring, Angela; Wichmann, H. Erich; Kolcic, Ivana; Zemunik, Tatijana; Boban, Mladen; Minelli, Cosetta; Wheeler, Heather E.; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H.; Wright, Alan F.; Campbell, Harry; Ellinghaus, David; Nöthlings, Ute; Jacobs, Gunnar; Biffar, Reiner; Endlich, Karlhans; Ernst, Florian; Homuth, Georg; Kroemer, Heyo K.; Nauck, Matthias; Stracke, Sylvia; Völker, Uwe; Völzke, Henry; Kovacs, Peter; Stumvoll, Michael; Mägi, Reedik; Hofman, Albert; Uitterlinden, Andre G.; Rivadeneira, Fernando; Aulchenko, Yurii S.; Polasek, Ozren; Hastie, Nick; Vitart, Veronique; Helmer, Catherine; Wang, Jie Jin; Ruggiero, Daniela; Bergmann, Sven; Kähönen, Mika; Viikari, Jorma; Nikopensius, Tiit; Province, Michael; Ketkar, Shamika; Colhoun, Helen; Doney, Alex; Robino, Antonietta; Giulianini, Franco; Krämer, Bernhard K.; Portas, Laura; Ford, Ian; Buckley, Brendan M.; Adam, Martin; Thun, Gian Andri; Paulweber, Bernhard; Haun, Margot; Sala, Cinzia; Metzger, Marie; Mitchell, Paul; Ciullo, Marina; Kim, Stuart K.; Vollenweider, Peter; Raitakari, Olli; Metspalu, Andres; Palmer, Colin; Gasparini, Paolo; Pirastu, Mario; Jukema, J. Wouter; Probst-Hensch, Nicole M.; Kronenberg, Florian; Toniolo, Daniela; Gudnason, Vilmundur; Shuldiner, Alan R.; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; Siscovick, David S.; van Duijn, Cornelia M.; Borecki, Ingrid; Kardia, Sharon L R; Liu, Yongmei; Curhan, Gary C.; Rudan, Igor; Gyllensten, Ulf; Wilson, James F.; Franke, Andre; Pramstaller, Peter P.; Rettig, Rainer; Prokopenko, Inga; Witteman, Jacqueline C M; Hayward, Caroline; Ridker, Paul; Parsa, Afshin; Bochud, Murielle; Heid, Iris M.; Goessling, Wolfram; Chasman, Daniel I.; Kao, W. H Linda; Fox, Caroline S.

In: PLoS Genetics, Vol. 8, No. 3, e1002584, 03.2012.

Research output: Contribution to journalArticle

Pattaro, C, Köttgen, A, Teumer, A, Garnaas, M, Böger, CA, Fuchsberger, C, Olden, M, Chen, MH, Tin, A, Taliun, D, Li, M, Gao, X, Gorski, M, Yang, Q, Hundertmark, C, Foster, MC, O'Seaghdha, CM, Glazer, N, Isaacs, A, Liu, CT, Smith, AV, O'Connell, JR, Struchalin, M, Tanaka, T, Li, G, Johnson, AD, Gierman, HJ, Feitosa, M, Hwang, SJ, Atkinson, EJ, Lohman, K, Cornelis, MC, Johansson, Å, Tönjes, A, Dehghan, A, Chouraki, V, Holliday, EG, Sorice, R, Kutalik, Z, Lehtimäki, T, Esko, T, Deshmukh, H, Ulivi, S, Chu, AY, Murgia, F, Trompet, S, Imboden, M, Kollerits, B, Pistis, G, Harris, TB, Launer, LJ, Aspelund, T, Eiriksdottir, G, Mitchell, BD, Boerwinkle, E, Schmidt, H, Cavalieri, M, Rao, M, Hu, FB, Demirkan, A, Oostra, BA, de Andrade, M, Turner, ST, Ding, J, Andrews, JS, Freedman, BI, Koenig, W, Illig, T, Döring, A, Wichmann, HE, Kolcic, I, Zemunik, T, Boban, M, Minelli, C, Wheeler, HE, Igl, W, Zaboli, G, Wild, SH, Wright, AF, Campbell, H, Ellinghaus, D, Nöthlings, U, Jacobs, G, Biffar, R, Endlich, K, Ernst, F, Homuth, G, Kroemer, HK, Nauck, M, Stracke, S, Völker, U, Völzke, H, Kovacs, P, Stumvoll, M, Mägi, R, Hofman, A, Uitterlinden, AG, Rivadeneira, F, Aulchenko, YS, Polasek, O, Hastie, N, Vitart, V, Helmer, C, Wang, JJ, Ruggiero, D, Bergmann, S, Kähönen, M, Viikari, J, Nikopensius, T, Province, M, Ketkar, S, Colhoun, H, Doney, A, Robino, A, Giulianini, F, Krämer, BK, Portas, L, Ford, I, Buckley, BM, Adam, M, Thun, GA, Paulweber, B, Haun, M, Sala, C, Metzger, M, Mitchell, P, Ciullo, M, Kim, SK, Vollenweider, P, Raitakari, O, Metspalu, A, Palmer, C, Gasparini, P, Pirastu, M, Jukema, JW, Probst-Hensch, NM, Kronenberg, F, Toniolo, D, Gudnason, V, Shuldiner, AR, Coresh, J, Schmidt, R, Ferrucci, L, Siscovick, DS, van Duijn, CM, Borecki, I, Kardia, SLR, Liu, Y, Curhan, GC, Rudan, I, Gyllensten, U, Wilson, JF, Franke, A, Pramstaller, PP, Rettig, R, Prokopenko, I, Witteman, JCM, Hayward, C, Ridker, P, Parsa, A, Bochud, M, Heid, IM, Goessling, W, Chasman, DI, Kao, WHL & Fox, CS 2012, 'Genome-wide association and functional follow-up reveals new loci for kidney function', PLoS Genetics, vol. 8, no. 3, e1002584. https://doi.org/10.1371/journal.pgen.1002584
Pattaro C, Köttgen A, Teumer A, Garnaas M, Böger CA, Fuchsberger C et al. Genome-wide association and functional follow-up reveals new loci for kidney function. PLoS Genetics. 2012 Mar;8(3). e1002584. https://doi.org/10.1371/journal.pgen.1002584
Pattaro, Cristian ; Köttgen, Anna ; Teumer, Alexander ; Garnaas, Maija ; Böger, Carsten A. ; Fuchsberger, Christian ; Olden, Matthias ; Chen, Ming Huei ; Tin, Adrienne ; Taliun, Daniel ; Li, Man ; Gao, Xiaoyi ; Gorski, Mathias ; Yang, Qiong ; Hundertmark, Claudia ; Foster, Meredith C. ; O'Seaghdha, Conall M. ; Glazer, Nicole ; Isaacs, Aaron ; Liu, Ching Ti ; Smith, Albert V. ; O'Connell, Jeffrey R. ; Struchalin, Maksim ; Tanaka, Toshiko ; Li, Guo ; Johnson, Andrew D. ; Gierman, Hinco J. ; Feitosa, Mary ; Hwang, Shih Jen ; Atkinson, Elizabeth J. ; Lohman, Kurt ; Cornelis, Marilyn C. ; Johansson, Åsa ; Tönjes, Anke ; Dehghan, Abbas ; Chouraki, Vincent ; Holliday, Elizabeth G. ; Sorice, Rossella ; Kutalik, Zoltan ; Lehtimäki, Terho ; Esko, Tõnu ; Deshmukh, Harshal ; Ulivi, Sheila ; Chu, Audrey Y. ; Murgia, Federico ; Trompet, Stella ; Imboden, Medea ; Kollerits, Barbara ; Pistis, Giorgio ; Harris, Tamara B. ; Launer, Lenore J. ; Aspelund, Thor ; Eiriksdottir, Gudny ; Mitchell, Braxton D. ; Boerwinkle, Eric ; Schmidt, Helena ; Cavalieri, Margherita ; Rao, Madhumathi ; Hu, Frank B. ; Demirkan, Ayse ; Oostra, Ben A. ; de Andrade, Mariza ; Turner, Stephen T. ; Ding, Jingzhong ; Andrews, Jeanette S. ; Freedman, Barry I. ; Koenig, Wolfgang ; Illig, Thomas ; Döring, Angela ; Wichmann, H. Erich ; Kolcic, Ivana ; Zemunik, Tatijana ; Boban, Mladen ; Minelli, Cosetta ; Wheeler, Heather E. ; Igl, Wilmar ; Zaboli, Ghazal ; Wild, Sarah H. ; Wright, Alan F. ; Campbell, Harry ; Ellinghaus, David ; Nöthlings, Ute ; Jacobs, Gunnar ; Biffar, Reiner ; Endlich, Karlhans ; Ernst, Florian ; Homuth, Georg ; Kroemer, Heyo K. ; Nauck, Matthias ; Stracke, Sylvia ; Völker, Uwe ; Völzke, Henry ; Kovacs, Peter ; Stumvoll, Michael ; Mägi, Reedik ; Hofman, Albert ; Uitterlinden, Andre G. ; Rivadeneira, Fernando ; Aulchenko, Yurii S. ; Polasek, Ozren ; Hastie, Nick ; Vitart, Veronique ; Helmer, Catherine ; Wang, Jie Jin ; Ruggiero, Daniela ; Bergmann, Sven ; Kähönen, Mika ; Viikari, Jorma ; Nikopensius, Tiit ; Province, Michael ; Ketkar, Shamika ; Colhoun, Helen ; Doney, Alex ; Robino, Antonietta ; Giulianini, Franco ; Krämer, Bernhard K. ; Portas, Laura ; Ford, Ian ; Buckley, Brendan M. ; Adam, Martin ; Thun, Gian Andri ; Paulweber, Bernhard ; Haun, Margot ; Sala, Cinzia ; Metzger, Marie ; Mitchell, Paul ; Ciullo, Marina ; Kim, Stuart K. ; Vollenweider, Peter ; Raitakari, Olli ; Metspalu, Andres ; Palmer, Colin ; Gasparini, Paolo ; Pirastu, Mario ; Jukema, J. Wouter ; Probst-Hensch, Nicole M. ; Kronenberg, Florian ; Toniolo, Daniela ; Gudnason, Vilmundur ; Shuldiner, Alan R. ; Coresh, Josef ; Schmidt, Reinhold ; Ferrucci, Luigi ; Siscovick, David S. ; van Duijn, Cornelia M. ; Borecki, Ingrid ; Kardia, Sharon L R ; Liu, Yongmei ; Curhan, Gary C. ; Rudan, Igor ; Gyllensten, Ulf ; Wilson, James F. ; Franke, Andre ; Pramstaller, Peter P. ; Rettig, Rainer ; Prokopenko, Inga ; Witteman, Jacqueline C M ; Hayward, Caroline ; Ridker, Paul ; Parsa, Afshin ; Bochud, Murielle ; Heid, Iris M. ; Goessling, Wolfram ; Chasman, Daniel I. ; Kao, W. H Linda ; Fox, Caroline S. / Genome-wide association and functional follow-up reveals new loci for kidney function. In: PLoS Genetics. 2012 ; Vol. 8, No. 3.
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title = "Genome-wide association and functional follow-up reveals new loci for kidney function",
abstract = "Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genome-wide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD.",
author = "Cristian Pattaro and Anna K{\"o}ttgen and Alexander Teumer and Maija Garnaas and B{\"o}ger, {Carsten A.} and Christian Fuchsberger and Matthias Olden and Chen, {Ming Huei} and Adrienne Tin and Daniel Taliun and Man Li and Xiaoyi Gao and Mathias Gorski and Qiong Yang and Claudia Hundertmark and Foster, {Meredith C.} and O'Seaghdha, {Conall M.} and Nicole Glazer and Aaron Isaacs and Liu, {Ching Ti} and Smith, {Albert V.} and O'Connell, {Jeffrey R.} and Maksim Struchalin and Toshiko Tanaka and Guo Li and Johnson, {Andrew D.} and Gierman, {Hinco J.} and Mary Feitosa and Hwang, {Shih Jen} and Atkinson, {Elizabeth J.} and Kurt Lohman and Cornelis, {Marilyn C.} and {\AA}sa Johansson and Anke T{\"o}njes and Abbas Dehghan and Vincent Chouraki and Holliday, {Elizabeth G.} and Rossella Sorice and Zoltan Kutalik and Terho Lehtim{\"a}ki and T{\~o}nu Esko and Harshal Deshmukh and Sheila Ulivi and Chu, {Audrey Y.} and Federico Murgia and Stella Trompet and Medea Imboden and Barbara Kollerits and Giorgio Pistis and Harris, {Tamara B.} and Launer, {Lenore J.} and Thor Aspelund and Gudny Eiriksdottir and Mitchell, {Braxton D.} and Eric Boerwinkle and Helena Schmidt and Margherita Cavalieri and Madhumathi Rao and Hu, {Frank B.} and Ayse Demirkan and Oostra, {Ben A.} and {de Andrade}, Mariza and Turner, {Stephen T.} and Jingzhong Ding and Andrews, {Jeanette S.} and Freedman, {Barry I.} and Wolfgang Koenig and Thomas Illig and Angela D{\"o}ring and Wichmann, {H. Erich} and Ivana Kolcic and Tatijana Zemunik and Mladen Boban and Cosetta Minelli and Wheeler, {Heather E.} and Wilmar Igl and Ghazal Zaboli and Wild, {Sarah H.} and Wright, {Alan F.} and Harry Campbell and David Ellinghaus and Ute N{\"o}thlings and Gunnar Jacobs and Reiner Biffar and Karlhans Endlich and Florian Ernst and Georg Homuth and Kroemer, {Heyo K.} and Matthias Nauck and Sylvia Stracke and Uwe V{\"o}lker and Henry V{\"o}lzke and Peter Kovacs and Michael Stumvoll and Reedik M{\"a}gi and Albert Hofman and Uitterlinden, {Andre G.} and Fernando Rivadeneira and Aulchenko, {Yurii S.} and Ozren Polasek and Nick Hastie and Veronique Vitart and Catherine Helmer and Wang, {Jie Jin} and Daniela Ruggiero and Sven Bergmann and Mika K{\"a}h{\"o}nen and Jorma Viikari and Tiit Nikopensius and Michael Province and Shamika Ketkar and Helen Colhoun and Alex Doney and Antonietta Robino and Franco Giulianini and Kr{\"a}mer, {Bernhard K.} and Laura Portas and Ian Ford and Buckley, {Brendan M.} and Martin Adam and Thun, {Gian Andri} and Bernhard Paulweber and Margot Haun and Cinzia Sala and Marie Metzger and Paul Mitchell and Marina Ciullo and Kim, {Stuart K.} and Peter Vollenweider and Olli Raitakari and Andres Metspalu and Colin Palmer and Paolo Gasparini and Mario Pirastu and Jukema, {J. Wouter} and Probst-Hensch, {Nicole M.} and Florian Kronenberg and Daniela Toniolo and Vilmundur Gudnason and Shuldiner, {Alan R.} and Josef Coresh and Reinhold Schmidt and Luigi Ferrucci and Siscovick, {David S.} and {van Duijn}, {Cornelia M.} and Ingrid Borecki and Kardia, {Sharon L R} and Yongmei Liu and Curhan, {Gary C.} and Igor Rudan and Ulf Gyllensten and Wilson, {James F.} and Andre Franke and Pramstaller, {Peter P.} and Rainer Rettig and Inga Prokopenko and Witteman, {Jacqueline C M} and Caroline Hayward and Paul Ridker and Afshin Parsa and Murielle Bochud and Heid, {Iris M.} and Wolfram Goessling and Chasman, {Daniel I.} and Kao, {W. H Linda} and Fox, {Caroline S.}",
year = "2012",
month = "3",
doi = "10.1371/journal.pgen.1002584",
language = "English (US)",
volume = "8",
journal = "PLoS Genetics",
issn = "1553-7390",
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}

TY - JOUR

T1 - Genome-wide association and functional follow-up reveals new loci for kidney function

AU - Pattaro, Cristian

AU - Köttgen, Anna

AU - Teumer, Alexander

AU - Garnaas, Maija

AU - Böger, Carsten A.

AU - Fuchsberger, Christian

AU - Olden, Matthias

AU - Chen, Ming Huei

AU - Tin, Adrienne

AU - Taliun, Daniel

AU - Li, Man

AU - Gao, Xiaoyi

AU - Gorski, Mathias

AU - Yang, Qiong

AU - Hundertmark, Claudia

AU - Foster, Meredith C.

AU - O'Seaghdha, Conall M.

AU - Glazer, Nicole

AU - Isaacs, Aaron

AU - Liu, Ching Ti

AU - Smith, Albert V.

AU - O'Connell, Jeffrey R.

AU - Struchalin, Maksim

AU - Tanaka, Toshiko

AU - Li, Guo

AU - Johnson, Andrew D.

AU - Gierman, Hinco J.

AU - Feitosa, Mary

AU - Hwang, Shih Jen

AU - Atkinson, Elizabeth J.

AU - Lohman, Kurt

AU - Cornelis, Marilyn C.

AU - Johansson, Åsa

AU - Tönjes, Anke

AU - Dehghan, Abbas

AU - Chouraki, Vincent

AU - Holliday, Elizabeth G.

AU - Sorice, Rossella

AU - Kutalik, Zoltan

AU - Lehtimäki, Terho

AU - Esko, Tõnu

AU - Deshmukh, Harshal

AU - Ulivi, Sheila

AU - Chu, Audrey Y.

AU - Murgia, Federico

AU - Trompet, Stella

AU - Imboden, Medea

AU - Kollerits, Barbara

AU - Pistis, Giorgio

AU - Harris, Tamara B.

AU - Launer, Lenore J.

AU - Aspelund, Thor

AU - Eiriksdottir, Gudny

AU - Mitchell, Braxton D.

AU - Boerwinkle, Eric

AU - Schmidt, Helena

AU - Cavalieri, Margherita

AU - Rao, Madhumathi

AU - Hu, Frank B.

AU - Demirkan, Ayse

AU - Oostra, Ben A.

AU - de Andrade, Mariza

AU - Turner, Stephen T.

AU - Ding, Jingzhong

AU - Andrews, Jeanette S.

AU - Freedman, Barry I.

AU - Koenig, Wolfgang

AU - Illig, Thomas

AU - Döring, Angela

AU - Wichmann, H. Erich

AU - Kolcic, Ivana

AU - Zemunik, Tatijana

AU - Boban, Mladen

AU - Minelli, Cosetta

AU - Wheeler, Heather E.

AU - Igl, Wilmar

AU - Zaboli, Ghazal

AU - Wild, Sarah H.

AU - Wright, Alan F.

AU - Campbell, Harry

AU - Ellinghaus, David

AU - Nöthlings, Ute

AU - Jacobs, Gunnar

AU - Biffar, Reiner

AU - Endlich, Karlhans

AU - Ernst, Florian

AU - Homuth, Georg

AU - Kroemer, Heyo K.

AU - Nauck, Matthias

AU - Stracke, Sylvia

AU - Völker, Uwe

AU - Völzke, Henry

AU - Kovacs, Peter

AU - Stumvoll, Michael

AU - Mägi, Reedik

AU - Hofman, Albert

AU - Uitterlinden, Andre G.

AU - Rivadeneira, Fernando

AU - Aulchenko, Yurii S.

AU - Polasek, Ozren

AU - Hastie, Nick

AU - Vitart, Veronique

AU - Helmer, Catherine

AU - Wang, Jie Jin

AU - Ruggiero, Daniela

AU - Bergmann, Sven

AU - Kähönen, Mika

AU - Viikari, Jorma

AU - Nikopensius, Tiit

AU - Province, Michael

AU - Ketkar, Shamika

AU - Colhoun, Helen

AU - Doney, Alex

AU - Robino, Antonietta

AU - Giulianini, Franco

AU - Krämer, Bernhard K.

AU - Portas, Laura

AU - Ford, Ian

AU - Buckley, Brendan M.

AU - Adam, Martin

AU - Thun, Gian Andri

AU - Paulweber, Bernhard

AU - Haun, Margot

AU - Sala, Cinzia

AU - Metzger, Marie

AU - Mitchell, Paul

AU - Ciullo, Marina

AU - Kim, Stuart K.

AU - Vollenweider, Peter

AU - Raitakari, Olli

AU - Metspalu, Andres

AU - Palmer, Colin

AU - Gasparini, Paolo

AU - Pirastu, Mario

AU - Jukema, J. Wouter

AU - Probst-Hensch, Nicole M.

AU - Kronenberg, Florian

AU - Toniolo, Daniela

AU - Gudnason, Vilmundur

AU - Shuldiner, Alan R.

AU - Coresh, Josef

AU - Schmidt, Reinhold

AU - Ferrucci, Luigi

AU - Siscovick, David S.

AU - van Duijn, Cornelia M.

AU - Borecki, Ingrid

AU - Kardia, Sharon L R

AU - Liu, Yongmei

AU - Curhan, Gary C.

AU - Rudan, Igor

AU - Gyllensten, Ulf

AU - Wilson, James F.

AU - Franke, Andre

AU - Pramstaller, Peter P.

AU - Rettig, Rainer

AU - Prokopenko, Inga

AU - Witteman, Jacqueline C M

AU - Hayward, Caroline

AU - Ridker, Paul

AU - Parsa, Afshin

AU - Bochud, Murielle

AU - Heid, Iris M.

AU - Goessling, Wolfram

AU - Chasman, Daniel I.

AU - Kao, W. H Linda

AU - Fox, Caroline S.

PY - 2012/3

Y1 - 2012/3

N2 - Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genome-wide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD.

AB - Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genome-wide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD.

UR - http://www.scopus.com/inward/record.url?scp=84859224378&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84859224378&partnerID=8YFLogxK

U2 - 10.1371/journal.pgen.1002584

DO - 10.1371/journal.pgen.1002584

M3 - Article

VL - 8

JO - PLoS Genetics

JF - PLoS Genetics

SN - 1553-7390

IS - 3

M1 - e1002584

ER -