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 language | English (US) |
|---|---|
| Article number | e1002584 |
| Journal | PLoS Genetics |
| Volume | 8 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 2012 |
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ASJC Scopus subject areas
- Genetics
- Molecular Biology
- Ecology, Evolution, Behavior and Systematics
- Cancer Research
- Genetics(clinical)
Cite this
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 journal › Article
}
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 -