Genome-Wide Association and Functional Follow-Up Reveals New Loci for Kidney Function

Pattaro, Cristian; Köttgen, Anna; Teumer, Alexander; 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.; Glazer, Nicole; Isaacs, Aaron; Liu, Ching-Ti; Smith, Albert V.; O'Connell, Jeffrey R.; Struchalin, Maksim; Tanaka, Toshiko; Gierman, Hinco J.; Feitosa, Mary; Hwang, Shih-Jen; Atkinson, Elizabeth J.; Lohman, Kurt; Johansson, Åsa; Tönjes, Anke; Dehghan, Abbas; Chouraki, Vincent; Holliday, Elizabeth G.; Sorice, Rossella; Kutalik, Zoltan; Lehtimäki, Terho; Esko, Tõnu; Deshmukh, Harshal; Ulivi, Sheila; 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; Demirkan, Ayse; Oostra, Ben A.; de Andrade, Mariza; 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; 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; Rudan, Igor; Gyllensten, Ulf; Wilson, James F.; Franke, Andre; Pramstaller, Peter P.; Rettig, Rainer; Prokopenko, Inga; Witteman, Jacqueline C. M.; Hayward, Caroline; Parsa, Afshin; Bochud, Murielle; Heid, Iris M.; Garnaas, Maija; O'Seaghdha, Conall; Li, Guo; Johnson, Andrew D.; Cornelis, Marilyn; Chu, Audrey Yu-lei; Hu, Frank B.; Turner, Stephen T.; Hofman, Albert; Curhan, Gary Craig; Ridker, Paul M.; Goessling, Wolfram; Chasman, Daniel Ian; Kao, W. H. Linda; Fox, Caroline

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Author

Pattaro, Cristian

Köttgen, Anna

Teumer, Alexander

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.

Glazer, Nicole

Isaacs, Aaron

Liu, Ching-Ti

Smith, Albert V.

O'Connell, Jeffrey R.

Struchalin, Maksim

Tanaka, Toshiko

Gierman, Hinco J.

Feitosa, Mary

Hwang, Shih-Jen

Atkinson, Elizabeth J.

Lohman, Kurt

Johansson, Åsa

Tönjes, Anke

Dehghan, Abbas

Chouraki, Vincent

Holliday, Elizabeth G.

Sorice, Rossella

Kutalik, Zoltan

Lehtimäki, Terho

Esko, Tõnu

Deshmukh, Harshal

Ulivi, Sheila

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

Demirkan, Ayse

Oostra, Ben A.

de Andrade, Mariza

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

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

Rudan, Igor

Gyllensten, Ulf

Wilson, James F.

Franke, Andre

Pramstaller, Peter P.

Rettig, Rainer

Prokopenko, Inga

Witteman, Jacqueline C. M.

Hayward, Caroline

Parsa, Afshin

Bochud, Murielle

Heid, Iris M.

Garnaas, Maija

O'Seaghdha, Conall HARVARD

Li, Guo

Johnson, Andrew D.

Cornelis, Marilyn HARVARD

Chu, Audrey Yu-lei HARVARD

Hu, Frank B. HARVARD

Turner, Stephen T.

Hofman, Albert HARVARD

Curhan, Gary Craig HARVARD

Ridker, Paul M. HARVARD

0000-0003-1249-4522

Goessling, Wolfram HARVARD

Chasman, Daniel Ian HARVARD

Kao, W. H. Linda

Fox, Caroline HARVARD

Note: Order does not necessarily reflect citation order of authors.

Published Version

https://doi.org/10.1371/journal.pgen.1002584

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Citation

Pattaro, Cristian, Anna Köttgen, Alexander Teumer, Maija Garnaas, Carsten A. Böger, Christian Fuchsberger, Matthias Olden, et al. 2012. Genome-wide association and functional follow-up reveals new loci for kidney function. PLoS Genetics 8(3): e1002584.

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.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3315455/pdf/

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