A catalog of genetic loci associated with kidney function from analyses of a million individuals

Wuttke, M; Li, Y; Li, M; Sieber, KB; Feitosa, MF; Gorski, M; Tin, A; Wang, L; Chu, AY; Hoppmann, A; Kirsten, H; Giri, A; Chai, J-F; Sveinbjornsson, G; Tayo, BO; Nutile, T; Fuchsberger, C; Marten, J; Cocca, M; Ghasemi, S; Xu, Y; Horn, K; Noce, D; Van der Most, PJ; Sedaghat, S; Yu, Z; Akiyama, M; Afaq, S; Ahluwalia, TS; Almgren, P; Amin, N; Arnlov, J; Bakker, SJL; Bansal, N; Baptista, D; Bergmann, S; Biggs, ML; Biino, G; Boehnke, M; Boerwinkle, E; Boissel, M; Bottinger, EP; Boutin, TS; Brenner, H; Brumat, M; Burkhardt, R; Butterworth, AS; Campana, E; Campbell, A; Campbell, H; Canouil, M; Carroll, RJ; Catamo, E; Chambers, JC; Chee, M-L; Chee, M-L; Chen, X; Cheng, C-Y; Cheng, Y; Christensen, K; Cifkova, R; Ciullo, M; Concas, MP; Cook, JP; Coresh, J; Corre, T; Sala, CF; Cusi, D; Danesh, J; Daw, EW; De Borst, MH; De Grandi, A; De Mutsert, R; De Vries, APJ; Degenhardt, F; Delgado, G; Demirkan, A; Di Angelantonio, E; Dittrich, K; Divers, J; Dorajoo, R; Eckardt, K-U; Ehret, G; Elliott, P; Endlich, K; Evans, MK; Felix, JF; Foo, VHX; Franco, OH; Franke, A; Freedman, BI; Freitag-Wolf, S; Friedlander, Y; Froguel, P; Gansevoort, RT; Gao, H; Gasparini, P; Gaziano, JM; Giedraitis, V; Gieger, C; Girotto, G; Giulianini, F; Gogele, M; Gordon, SD; Gudbjartsson, DF; Gudnason, V; Haller, T; Hamet, P; Harris, TB; Hartman, CA; Hayward, C; Hellwege, JN; Heng, C-K; Hicks, AA; Hofer, E; Huang, W; Hutri-Kahonen, N; Hwang, S-J; Ikram, MA; Indridason, OS; Ingelsson, E; Ising, M; Jaddoe, VWV; Jakobsdottir, J; Jonas, JB; Joshi, PK; Josyula, NS; Jung, B; Kahonen, M; Kamatani, Y; Kammerer, CM; Kanai, M; Kastarinen, M; Kerr, SM; Khor, C-C; Kiess, W; Kleber, ME; Koenig, W; Kooner, JS; Korner, A; Kovacs, P; Kraja, AT; Krajcoviechova, A; Kramer, H; Kramer, BK; Kronenberg, F; Kubo, M; Kuhnel, B; Kuokkanen, M; Kuusisto, J; La Bianca, M; Laakso, M; Lange, LA; Langefeld, CD; Lee, JJ-M; Lehne, B; Lehtimaki, T; Lieb, W; Lim, S-C; Lind, L; Lindgren, CM; Liu, J; Liu, J; Loeffler, M; Loos, RJF; Lucae, S; Lukas, MA; Lyytikainen, L-P; Magi, R; Magnusson, PKE; Mahajan, A; Martin, NG; Martins, J; Marz, W; Mascalzoni, D; Matsuda, K; Meisinger, C; Meitinger, T; Melander, O; Metspalu, A; Mikaelsdottir, EK; Milaneschi, Y; Miliku, K; Mishra, PP; Program, VAMV; Mohlke, KL; Mononen, N; Montgomery, GW; Mook-Kanamori, DO; Mychaleckyj, JC; Nadkarni, GN; Nalls, MA; Nauck, M; Nikus, K; Ning, B; Nolte, IM; Noordam, R; O'Connell, J; O'Donoghue, ML; Olafsson, I; Oldehinkel, AJ; Orho-Melander, M; Ouwehand, WH; Padmanabhan, S; Palmer, ND; Palsson, R; Penninx, BWJH; Perls, T; Perola, M; Pirastu, M; Pirastu, N; Pistis, G; Podgornaia, AI; Polasek, O; Ponte, B; Porteous, DJ; Poulain, T; Pramstaller, PP; Preuss, MH; Prins, BP; Province, MA; Rabelink, TJ; Raffield, LM; Raitakari, OT; Reilly, DF; Rettig, R; Rheinberger, M; Rice, KM; Ridker, PM; Rivadeneira, F; Rizzi, F; Roberts, DJ; Robino, A; Rossing, P; Rudan, I; Rueedi, R; Ruggiero, D; Ryan, KA; Saba, Y; Sabanayagam, C; Salomaa, V; Salvi, E; Saum, K-U; Schmidt, H; Schmidt, R; Ben, S; Schulz, C-A; Schupf, N; Shaffer, CM; Shi, Y; Smith, AV; Smith, BH; Soranzo, N; Spracklen, CN; Strauch, K; Stringham, HM; Stumvoll, M; Svensson, PO; Szymczak, S; Tai, E-S; Tajuddin, SM; Tan, NYQ; Taylor, KD; Teren, A; Tham, Y-C; Thiery, J; Thio, CHL; Thomsen, H; Thorleifsson, G; Toniolo, D; Tonjes, A; Tremblay, J; Tzoulaki, I; Uitterlinden, AG; Vaccargiu, S; Van Dam, RM; Van der Harst, P; Van Duijn, CM; Edward, DRV; Verweij, N; Vogelezang, S; Volker, U; Vollenweider, P; Waeber, G; Waldenberger, M; Wallentin, L; Wang, YX; Wang, C; Waterworth, DM; Bin Wei, W; White, H; Whitfield, JB; Wild, SH; Wilson, JF; Wojczynski, MK; Wong, C; Wong, T-Y; Xu, L; Yang, Q; Yasuda, M; Yerges-Armstrong, LM; Zhang, W; Zonderman, AB; Rotter, JI; Bochud, M; Psaty, BM; Vitart, V; Wilson, JG; Dehghan, A; Parsa, A; Chasman, DI; Ho, K; Morris, AP; Devuyst, O; Akilesh, S; Pendergrass, SA; Sim, X; Boger, CA; Okada, Y; Edwards, TL; Snieder, H; Stefansson, K; Hung, AM; Heid, IM; Scholz, M; Teumer, A; Kottgen, A; Pattaro, C

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A catalog of genetic loci associated with kidney function from analyses of a million individuals

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Title:	A catalog of genetic loci associated with kidney function from analyses of a million individuals
Authors:	Wuttke, M Li, Y Li, M Sieber, KB Feitosa, MF Gorski, M Tin, A Wang, L Chu, AY Hoppmann, A Kirsten, H Giri, A Chai, J-F Sveinbjornsson, G Tayo, BO Nutile, T Fuchsberger, C Marten, J Cocca, M Ghasemi, S Xu, Y Horn, K Noce, D Van der Most, PJ Sedaghat, S Yu, Z Akiyama, M Afaq, S Ahluwalia, TS Almgren, P Amin, N Arnlov, J Bakker, SJL Bansal, N Baptista, D Bergmann, S Biggs, ML Biino, G Boehnke, M Boerwinkle, E Boissel, M Bottinger, EP Boutin, TS Brenner, H Brumat, M Burkhardt, R Butterworth, AS Campana, E Campbell, A Campbell, H Canouil, M Carroll, RJ Catamo, E Chambers, JC Chee, M-L Chee, M-L Chen, X Cheng, C-Y Cheng, Y Christensen, K Cifkova, R Ciullo, M Concas, MP Cook, JP Coresh, J Corre, T Sala, CF Cusi, D Danesh, J Daw, EW De Borst, MH De Grandi, A De Mutsert, R De Vries, APJ Degenhardt, F Delgado, G Demirkan, A Di Angelantonio, E Dittrich, K Divers, J Dorajoo, R Eckardt, K-U Ehret, G Elliott, P Endlich, K Evans, MK Felix, JF Foo, VHX Franco, OH Franke, A Freedman, BI Freitag-Wolf, S Friedlander, Y Froguel, P Gansevoort, RT Gao, H Gasparini, P Gaziano, JM Giedraitis, V Gieger, C Girotto, G Giulianini, F Gogele, M Gordon, SD Gudbjartsson, DF Gudnason, V Haller, T Hamet, P Harris, TB Hartman, CA Hayward, C Hellwege, JN Heng, C-K Hicks, AA Hofer, E Huang, W Hutri-Kahonen, N Hwang, S-J Ikram, MA Indridason, OS Ingelsson, E Ising, M Jaddoe, VWV Jakobsdottir, J Jonas, JB Joshi, PK Josyula, NS Jung, B Kahonen, M Kamatani, Y Kammerer, CM Kanai, M Kastarinen, M Kerr, SM Khor, C-C Kiess, W Kleber, ME Koenig, W Kooner, JS Korner, A Kovacs, P Kraja, AT Krajcoviechova, A Kramer, H Kramer, BK Kronenberg, F Kubo, M Kuhnel, B Kuokkanen, M Kuusisto, J La Bianca, M Laakso, M Lange, LA Langefeld, CD Lee, JJ-M Lehne, B Lehtimaki, T Lieb, W Lim, S-C Lind, L Lindgren, CM Liu, J Liu, J Loeffler, M Loos, RJF Lucae, S Lukas, MA Lyytikainen, L-P Magi, R Magnusson, PKE Mahajan, A Martin, NG Martins, J Marz, W Mascalzoni, D Matsuda, K Meisinger, C Meitinger, T Melander, O Metspalu, A Mikaelsdottir, EK Milaneschi, Y Miliku, K Mishra, PP Program, VAMV Mohlke, KL Mononen, N Montgomery, GW Mook-Kanamori, DO Mychaleckyj, JC Nadkarni, GN Nalls, MA Nauck, M Nikus, K Ning, B Nolte, IM Noordam, R O'Connell, J O'Donoghue, ML Olafsson, I Oldehinkel, AJ Orho-Melander, M Ouwehand, WH Padmanabhan, S Palmer, ND Palsson, R Penninx, BWJH Perls, T Perola, M Pirastu, M Pirastu, N Pistis, G Podgornaia, AI Polasek, O Ponte, B Porteous, DJ Poulain, T Pramstaller, PP Preuss, MH Prins, BP Province, MA Rabelink, TJ Raffield, LM Raitakari, OT Reilly, DF Rettig, R Rheinberger, M Rice, KM Ridker, PM Rivadeneira, F Rizzi, F Roberts, DJ Robino, A Rossing, P Rudan, I Rueedi, R Ruggiero, D Ryan, KA Saba, Y Sabanayagam, C Salomaa, V Salvi, E Saum, K-U Schmidt, H Schmidt, R Ben, S Schulz, C-A Schupf, N Shaffer, CM Shi, Y Smith, AV Smith, BH Soranzo, N Spracklen, CN Strauch, K Stringham, HM Stumvoll, M Svensson, PO Szymczak, S Tai, E-S Tajuddin, SM Tan, NYQ Taylor, KD Teren, A Tham, Y-C Thiery, J Thio, CHL Thomsen, H Thorleifsson, G Toniolo, D Tonjes, A Tremblay, J Tzoulaki, I Uitterlinden, AG Vaccargiu, S Van Dam, RM Van der Harst, P Van Duijn, CM Edward, DRV Verweij, N Vogelezang, S Volker, U Vollenweider, P Waeber, G Waldenberger, M Wallentin, L Wang, YX Wang, C Waterworth, DM Bin Wei, W White, H Whitfield, JB Wild, SH Wilson, JF Wojczynski, MK Wong, C Wong, T-Y Xu, L Yang, Q Yasuda, M Yerges-Armstrong, LM Zhang, W Zonderman, AB Rotter, JI Bochud, M Psaty, BM Vitart, V Wilson, JG Dehghan, A Parsa, A Chasman, DI Ho, K Morris, AP Devuyst, O Akilesh, S Pendergrass, SA Sim, X Boger, CA Okada, Y Edwards, TL Snieder, H Stefansson, K Hung, AM Heid, IM Scholz, M Teumer, A Kottgen, A Pattaro, C
Item Type:	Journal Article
Abstract:	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.
Issue Date:	31-May-2019
Date of Acceptance:	29-Mar-2019
URI:	http://hdl.handle.net/10044/1/70965
DOI:	https://doi.org/10.1038/s41588-019-0407-x
ISSN:	1061-4036
Publisher:	Nature Research
Start Page:	957
End Page:	972
Journal / Book Title:	Nature Genetics
Volume:	51
Issue:	6
Copyright Statement:	© 2019 Springer-Verlag. The final publication is available at Springer via https://doi.org/10.1038/s41588-019-0407-x.
Keywords:	Science & Technology Life Sciences & Biomedicine Genetics & Heredity GENOME-WIDE ASSOCIATION COMMON VARIANTS RENAL-FUNCTION TRANS-EQTLS DISEASE METAANALYSIS TRANSPORTER CLASSIFICATION HERITABILITY INTEGRATION Lifelines Cohort Study V. A. Million Veteran Program Science & Technology Life Sciences & Biomedicine Genetics & Heredity GENOME-WIDE ASSOCIATION COMMON VARIANTS RENAL-FUNCTION TRANS-EQTLS DISEASE METAANALYSIS TRANSPORTER CLASSIFICATION HERITABILITY INTEGRATION Developmental Biology 11 Medical and Health Sciences 06 Biological Sciences
Publication Status:	Published
Online Publication Date:	2019-05-31
Appears in Collections:	School of Public Health