Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 957-972 |
| Number of pages | 16 |
| Journal | Nature Genetics |
| Volume | 51 |
| Issue number | 6 |
| Early online date | 31 May 2019 |
| DOIs | |
| Publication status | Published - Jun 2019 |
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A catalog of genetic loci associated with kidney function from analyses of a million individuals. / Wuttke, Matthias; Li, Yong; Li, Man; Sieber, Karsten B.; Feitosa, Mary F; Gorski, Mathias; Tin, Adrienne; Wang, Lihua; Chu, Audrey Y; Hoppmann, Anselm; Kirsten, Holger; Giri, Ayush; Chai, Jin Fang; Sveinbjornsson, Gardar; Tayo, Bamidele O; Nutile, Teresa; Fuchsberger, Christian; Marten, Jonathan; Cocca, Massimiliano; Ghasemi, Sahar; Xu, Yizhe; Horn, Katrin; Noce, Damia; van der Most, Peter J; Sedaghat, Sanaz; Yu, Zhi; Akiyama, Masato; Afaq, Saima; Ahluwalia, Tarunveer S; Almgren, Peter; Amin, Najaf; Ärnlöv, Johan; Bakker, Stephan J. L.; Bansal, Nisha; Baptista, Daniela; Bergmann, Sven; Biggs , Mary L.; Biino, Ginevra; Boehnke, Michael; Boerwinkle, Eric; Boissel, Mathilde; Bottinger, Erwin P.; Boutin, Thibaud; Brenner, Hermann; Brumat, Marco; Campbell, Archie; Campbell, Harry; Hayward, Caroline; Joshi, Peter K.; Kerr, Shona; LifeLines Cohort Study; Lim, Su-Chi; Lind, Lars; Lindgren, Cecilia M.; Liu, Jun; Liu, Jianjun; Loeffler, Markus; Loos, Ruth J. F.; Lucae, Susanne; Lukas, Mary Ann; Lyytikäinen, Leo-Pekka; Mägi, Reedik; Magnusson, Patrik K. E.; Mahajan, Anubha; Martin, Nicholas G.; Martins, Jade; März, Winfried; Mascalzoni, Deborah; Matsuda, Koichi; Meisinger, Christa; Meitinger, Thomas; Melander, Olle; Metspalu, Andres; Mikaelsdottir, Evgenia K.; Milaneschi, Yuri; Miliku, Kozeta; Mishra, Pashupati P; V. A. Million Veteran Program; Mohlke, Karen L.; Montgomery, Grant W.; Mychaleckyj, Josyf C.; Nadkarni, Girish N.; Nalls, Mike A.; Nauck, Matthias; Nikus, Kjell; Ning, Boting; Nolte, Ilja M.; Noordam, Raymond; O’Connell, Jeffrey R.; O'Donoghue, Michelle L.; Olafsson, Isleifur; Oldehinkel, Albertine J; Orho-Melander, Marju; Ouwehand, Willem H.; Padmanabhan, Sandosh; Palmer, Nicholette D.; Palsson, Runolfur; Penninx, Brenda W. J. H.; Perls, Thomas; Perola, Markus; Pirastu, Mario; Pirastu, Nicola; Pistis, Giorgio; Podgornaia, Anna I.; Polasek, Ozren; Ponte, Belen; Porteous, David J.; Poulain, Tanja; Pramstaller, Peter P.; Preuss, Michael H.; Prins, Bram P.; Province, Michael A.; Rabelink, Ton J.; Raffield, Laura M.; Raitakari, Olli T.; Reilly, Dermot F.; Rettig, Rainer; Rheinberger, Myriam; Rice, Kenneth M.; Ridker, Paul M.; Rivadeneira, Fernando; Rizzi, Federica; Roberts, David J.; Robino, Antonietta; Rossing, Peter; Rudan, Igor; Rueedi, Rico ; Ruggiero, Daniela; Ryan, Kathleen A.; Saba, Yasaman; Sabanayagam, Charumathi; Salomaa, Veikko; Salvi, Erika; Saum, Kai-Uwe; Schmidt, Helena; Schmidt, Reinhold; Schöttker, Ben; Schulz, Christina-Alexandra; Schupf, Nicole; Shaffer, Christian M.; Shi, Yuan; Smith, Albert V.; Smith, Blair H.; Soranzo, Nicole; Spracklen, Cassandra N.; Strauch, Konstantin; Stringham, Heather M.; Stumvoll, Michael; Svensson, Per O.; Szymczak, Silke; Tai, E-Shyong; Tajuddin, Salman M.; Tan, Nicholas Y. Q.; Taylor, Kent D.; Teren, Andrej; Tham, Yih-Chung; Thiery, Joachim; Thio, Chris H. L.; Thomsen, Hauke; Thorleifsson, Gudmar; Toniolo, Daniela; Tönjes, Anke; Tremblay, Johanne; Tzoulaki, Ioanna; Uitterlinden, André G; Vaccargiu, Simona; van Dam, Rob M.; van der Harst, Pim; van Duijn, Cornelia M.; Velez Edwards, Digna R.; Verweij, Niek; Vogelezang, Suzanne; Völker, Uwe; Vollenweider, Peter; Waeber, Gerard ; Waldenberger, Melanie; Wallentin, Lars; Wang, Ya Xing; Wang, Chaolong; Waterworth, Dawn M.; Wei, Wen Bin; White, Harvey; Whitfield, John B.; Wild, Sarah H.; Wilson, James F.; Wojczynski, Mary K.; Wong, Charlene; Wong, Tien-Yin; Xu, Liang; Yang, Qiong; Yasuda, Masayuki; Yerges-Armstrong, Laura M.; Zhang, Weihua; Zonderman, Alan B.; Rotter, Jerome I.; Bochud, Murielle; Psaty, Bruce M.; Vitart, Veronique; Wilson, James G.; Dehghan, Abbas; Parsa, Afshin; Chasman, Daniel I.; Ho, Kevin; Morris, Andrew P.; Devuyst, Olivier; Akilesh, Shreeram; Pendergrass, Sarah A.; Sim, Xueling; Böger, Carsten A.; Okada, Yukinori; Edwards, Todd L.; Snieder, Harold; Stefansson, Kari; Hung, Adriana M.; Heid, Iris M.; Scholz, Markus; Teumer, Alexander; Köttgen, Anna; Pattaro, Cristian.
In: Nature Genetics, Vol. 51, No. 6, 06.2019, p. 957-972.Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - A catalog of genetic loci associated with kidney function from analyses of a million individuals
AU - Wuttke, Matthias
AU - Li, Yong
AU - Li, Man
AU - Sieber, Karsten B.
AU - Feitosa, Mary F
AU - Gorski, Mathias
AU - Tin, Adrienne
AU - Wang, Lihua
AU - Chu, Audrey Y
AU - Hoppmann, Anselm
AU - Kirsten, Holger
AU - Giri, Ayush
AU - Chai, Jin Fang
AU - Sveinbjornsson, Gardar
AU - Tayo, Bamidele O
AU - Nutile, Teresa
AU - Fuchsberger, Christian
AU - Marten, Jonathan
AU - Cocca, Massimiliano
AU - Ghasemi, Sahar
AU - Xu, Yizhe
AU - Horn, Katrin
AU - Noce, Damia
AU - van der Most, Peter J
AU - Sedaghat, Sanaz
AU - Yu, Zhi
AU - Akiyama, Masato
AU - Afaq, Saima
AU - Ahluwalia, Tarunveer S
AU - Almgren, Peter
AU - Amin, Najaf
AU - Ärnlöv, Johan
AU - Bakker, Stephan J. L.
AU - Bansal, Nisha
AU - Baptista, Daniela
AU - Bergmann, Sven
AU - Biggs , Mary L.
AU - Biino, Ginevra
AU - Boehnke, Michael
AU - Boerwinkle, Eric
AU - Boissel, Mathilde
AU - Bottinger, Erwin P.
AU - Boutin, Thibaud
AU - Brenner, Hermann
AU - Brumat, Marco
AU - Campbell, Archie
AU - Campbell, Harry
AU - Hayward, Caroline
AU - Joshi, Peter K.
AU - Kerr, Shona
AU - LifeLines Cohort Study
AU - Lim, Su-Chi
AU - Lind, Lars
AU - Lindgren, Cecilia M.
AU - Liu, Jun
AU - Liu, Jianjun
AU - Loeffler, Markus
AU - Loos, Ruth J. F.
AU - Lucae, Susanne
AU - Lukas, Mary Ann
AU - Lyytikäinen, Leo-Pekka
AU - Mägi, Reedik
AU - Magnusson, Patrik K. E.
AU - Mahajan, Anubha
AU - Martin, Nicholas G.
AU - Martins, Jade
AU - März, Winfried
AU - Mascalzoni, Deborah
AU - Matsuda, Koichi
AU - Meisinger, Christa
AU - Meitinger, Thomas
AU - Melander, Olle
AU - Metspalu, Andres
AU - Mikaelsdottir, Evgenia K.
AU - Milaneschi, Yuri
AU - Miliku, Kozeta
AU - Mishra, Pashupati P
AU - V. A. Million Veteran Program
AU - Mohlke, Karen L.
AU - Montgomery, Grant W.
AU - Mychaleckyj, Josyf C.
AU - Nadkarni, Girish N.
AU - Nalls, Mike A.
AU - Nauck, Matthias
AU - Nikus, Kjell
AU - Ning, Boting
AU - Nolte, Ilja M.
AU - Noordam, Raymond
AU - O’Connell, Jeffrey R.
AU - O'Donoghue, Michelle L.
AU - Olafsson, Isleifur
AU - Oldehinkel, Albertine J
AU - Orho-Melander, Marju
AU - Ouwehand, Willem H.
AU - Padmanabhan, Sandosh
AU - Palmer, Nicholette D.
AU - Palsson, Runolfur
AU - Penninx, Brenda W. J. H.
AU - Perls, Thomas
AU - Perola, Markus
AU - Pirastu, Mario
AU - Pirastu, Nicola
AU - Pistis, Giorgio
AU - Podgornaia, Anna I.
AU - Polasek, Ozren
AU - Ponte, Belen
AU - Porteous, David J.
AU - Poulain, Tanja
AU - Pramstaller, Peter P.
AU - Preuss, Michael H.
AU - Prins, Bram P.
AU - Province, Michael A.
AU - Rabelink, Ton J.
AU - Raffield, Laura M.
AU - Raitakari, Olli T.
AU - Reilly, Dermot F.
AU - Rettig, Rainer
AU - Rheinberger, Myriam
AU - Rice, Kenneth M.
AU - Ridker, Paul M.
AU - Rivadeneira, Fernando
AU - Rizzi, Federica
AU - Roberts, David J.
AU - Robino, Antonietta
AU - Rossing, Peter
AU - Rudan, Igor
AU - Rueedi, Rico
AU - Ruggiero, Daniela
AU - Ryan, Kathleen A.
AU - Saba, Yasaman
AU - Sabanayagam, Charumathi
AU - Salomaa, Veikko
AU - Salvi, Erika
AU - Saum, Kai-Uwe
AU - Schmidt, Helena
AU - Schmidt, Reinhold
AU - Schöttker, Ben
AU - Schulz, Christina-Alexandra
AU - Schupf, Nicole
AU - Shaffer, Christian M.
AU - Shi, Yuan
AU - Smith, Albert V.
AU - Smith, Blair H.
AU - Soranzo, Nicole
AU - Spracklen, Cassandra N.
AU - Strauch, Konstantin
AU - Stringham, Heather M.
AU - Stumvoll, Michael
AU - Svensson, Per O.
AU - Szymczak, Silke
AU - Tai, E-Shyong
AU - Tajuddin, Salman M.
AU - Tan, Nicholas Y. Q.
AU - Taylor, Kent D.
AU - Teren, Andrej
AU - Tham, Yih-Chung
AU - Thiery, Joachim
AU - Thio, Chris H. L.
AU - Thomsen, Hauke
AU - Thorleifsson, Gudmar
AU - Toniolo, Daniela
AU - Tönjes, Anke
AU - Tremblay, Johanne
AU - Tzoulaki, Ioanna
AU - Uitterlinden, André G
AU - Vaccargiu, Simona
AU - van Dam, Rob M.
AU - van der Harst, Pim
AU - van Duijn, Cornelia M.
AU - Velez Edwards, Digna R.
AU - Verweij, Niek
AU - Vogelezang, Suzanne
AU - Völker, Uwe
AU - Vollenweider, Peter
AU - Waeber, Gerard
AU - Waldenberger, Melanie
AU - Wallentin, Lars
AU - Wang, Ya Xing
AU - Wang, Chaolong
AU - Waterworth, Dawn M.
AU - Wei, Wen Bin
AU - White, Harvey
AU - Whitfield, John B.
AU - Wild, Sarah H.
AU - Wilson, James F.
AU - Wojczynski, Mary K.
AU - Wong, Charlene
AU - Wong, Tien-Yin
AU - Xu, Liang
AU - Yang, Qiong
AU - Yasuda, Masayuki
AU - Yerges-Armstrong, Laura M.
AU - Zhang, Weihua
AU - Zonderman, Alan B.
AU - Rotter, Jerome I.
AU - Bochud, Murielle
AU - Psaty, Bruce M.
AU - Vitart, Veronique
AU - Wilson, James G.
AU - Dehghan, Abbas
AU - Parsa, Afshin
AU - Chasman, Daniel I.
AU - Ho, Kevin
AU - Morris, Andrew P.
AU - Devuyst, Olivier
AU - Akilesh, Shreeram
AU - Pendergrass, Sarah A.
AU - Sim, Xueling
AU - Böger, Carsten A.
AU - Okada, Yukinori
AU - Edwards, Todd L.
AU - Snieder, Harold
AU - Stefansson, Kari
AU - Hung, Adriana M.
AU - Heid, Iris M.
AU - Scholz, Markus
AU - Teumer, Alexander
AU - Köttgen, Anna
AU - Pattaro, Cristian
PY - 2019/6
Y1 - 2019/6
N2 - Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
AB - Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
U2 - 10.1038/s41588-019-0407-x
DO - 10.1038/s41588-019-0407-x
M3 - Article
C2 - 31152163
VL - 51
SP - 957
EP - 972
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 6
ER -