Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals

Winkler, TW; Rasheed, H; Teumer, A; Gorski, M; Rowan, BX; Stanzick, KJ; Thomas, LF; Tin, A; Hoppmann, A; Chu, AY; Tayo, B; Thio, CHL; Cusi, D; Chai, J-F; Sieber, KB; Horn, K; Li, M; Scholz, M; Cocca, M; Wuttke, M; Van der Most, PJ; Yang, Q; Ghasemi, S; Nutile, T; Li, Y; Pontali, G; Guenther, F; Dehghan, A; Correa, A; Parsa, A; Feresin, A; De Vries, APJ; Zonderman, AB; Smith, A; Oldehinkel, AJ; De Grandi, A; Rosenkranz, AR; Franke, A; Teren, A; Metspalu, A; Hicks, AA; Morris, AP; Toenjes, A; Morgan, A; Podgornaia, A; Peters, A; Koerner, A; Mahajan, A; Campbell, A; Freedman, B; Spedicati, B; Ponte, B; Schoettker, B; Brumpton, B; Banas, B; Kraemer, BK; Jung, B; Asvold, BO; Smith, BH; Ning, B; Penninx, BWJH; Vanderwerff, BR; Psaty, BM; Kammerer, CM; Langefeld, CD; Hayward, C; Spracklen, CN; Robinson-Cohen, C; Hartman, CA; Lindgren, CM; Wang, C; Sabanayagam, C; Heng, C-K; Lanzani, C; Khor, C-C; Cheng, C-Y; Fuchsberger, C; Gieger, C; Shaffer, CM; Schulz, C-A; Willer, CJ; Chasman, D; Gudbjartsson, DF; Ruggiero, D; Toniolo, D; Czamara, D; Porteous, DJ; Waterworth, DM; Mascalzoni, D; Mook-Kanamori, DO; Reilly, DF; Daw, EW; Hofer, E; Boerwinkle, E; Salvi, E; Bottinger, EP; Tai, E-S; Catamo, E; Rizzi, F; Guo, F; Rivadeneira, F; Guilianini, F; Sveinbjornsson, G; Ehret, G; Waeber, G; Biino, G; Girotto, G; Pistis, G; Nadkarni, GN; Delgado, GE; Montgomery, GW; Snieder, H; Campbell, H; White, HD; Gao, H; Stringham, HM; Schmidt, H; Li, H; Brenner, H; Holm, H; Kirsten, H; Kramer, H; Rudan, I; Nolte, IM; Tzoulaki, I; Olafsson, I; Martins, J; Cook, JP; Wilson, JF; Halbritter, J; Felix, JF; Divers, J; Kooner, JS; Lee, JJ-M; O'Connell, J; Rotter, J; Liu, J; Xu, J; Thiery, J; Arnlov, J; Kuusisto, J; Jakobsdottir, J; Tremblay, J; Chambers, JC; Whitfield, JB; Gaziano, JM; Marten, J; Coresh, J; Jonas, JB; Mychaleckyj, JC; Christensen, K; Eckardt, K-U; Mohlke, KL; Endlich, K; Dittrich, K; Ryan, KA; Rice, KM; Taylor, KD; Ho, K; Nikus, K; Matsuda, K; Strauch, K; Miliku, K; Hveem, K; Lind, L; Wallentin, L; Yerges-Armstrong, LM; Raffield, LM; Phillips, LS; Launer, LJ; Lyytikainen, L-P; Lange, LA; Citterio, L; Klaric, L; Ikram, MA; Ising, M; Kleber, ME; Francescatto, M; Concas, MP; Ciullo, M; Piratsu, M; Orho-Melander, M; Laakso, M; Loeffler, M; Perola, M; De Borst, MH; Gogele, M; La Bianca, M; Lukas, MA; Feitosa, MF; Biggs, ML; Wojczynski, MK; Kavousi, M; Kanai, M; Akiyama, M; Yasuda, M; Nauck, M; Waldenberger, M; Chee, M-L; Chee, M-L; Boehnke, M; Preuss, MH; Stumvoll, M; Province, MA; Evans, MK; O'Donoghue, ML; Kubo, M; Kahonen, M; Kastarinen, M; Nalls, MA; Kuokkanen, M; Ghanbari, M; Bochud, M; Josyula, NS; Martin, NG; Tan, NYQ; Palmer, ND; Pirastu, N; Schupf, N; Verweij, N; Hutri-Kahonen, N; Mononen, N; Bansal, N; Devuyst, O; Melander, O; Raitakari, OT; Polasek, O; Manunta, P; Gasparini, P; Mishra, PP; Sulem, P; Magnusson, PKE; Elliott, P; Ridker, PM; Hamet, P; Svensson, PO; Joshi, PK; Kovacs, P; Pramstaller, PP; Rossing, P; Vollenweider, P; Van der Harst, P; Dorajoo, R; Sim, RZH; Burkhardt, R; Tao, R; Noordam, R; Magi, R; Schmidt, R; De Mutsert, R; Rueedi, R; Van Dam, RM; Carroll, RJ; Gansevoort, RT; Loos, RJF; Felicita, SC; Sedaghat, S; Padmanabhan, S; Freitag-Wolf, S; Pendergrass, SA; Graham, SE; Gordon, SD; Hwang, S-J; Kerr, SM; Vaccargiu, S; Patil, SB; Hallan, S; Bakker, SJL; Lim, S-C; Lucae, S; Vogelezang, S; Bergmann, S; Corre, T; Ahluwalia, TS; Lehtimaki, T; Boutin, TS; Meitinger, T; Wong, T-Y; Bergler, T; Rabelink, TJ; Esko, T; Haller, T; Thorsteinsdottir, U; Voelker, U; Foo, VHX; Salomaa, V; Vitart, V; Giedraitis, V; Gudnason, V; Jaddoe, VWV; Huang, W; Zhang, W; Wei, WB; Kiess, W; Marz, W; Koenig, W; Lieb, W; Gao, X; Sim, X; Wang, YX; Friedlander, Y; Tham, Y-C; Kamatani, Y; Okada, Y; Milaneschi, Y; Yu, Z; Stark, KJ; Stefansson, K; Boeger, CA; Hung, AM; Kronenberg, F; Koettgen, A; Pattaro, C; Heid, IM

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Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals

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Title:	Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals
Authors:	Winkler, TW Rasheed, H Teumer, A Gorski, M Rowan, BX Stanzick, KJ Thomas, LF Tin, A Hoppmann, A Chu, AY Tayo, B Thio, CHL Cusi, D Chai, J-F Sieber, KB Horn, K Li, M Scholz, M Cocca, M Wuttke, M Van der Most, PJ Yang, Q Ghasemi, S Nutile, T Li, Y Pontali, G Guenther, F Dehghan, A Correa, A Parsa, A Feresin, A De Vries, APJ Zonderman, AB Smith, A Oldehinkel, AJ De Grandi, A Rosenkranz, AR Franke, A Teren, A Metspalu, A Hicks, AA Morris, AP Toenjes, A Morgan, A Podgornaia, A Peters, A Koerner, A Mahajan, A Campbell, A Freedman, B Spedicati, B Ponte, B Schoettker, B Brumpton, B Banas, B Kraemer, BK Jung, B Asvold, BO Smith, BH Ning, B Penninx, BWJH Vanderwerff, BR Psaty, BM Kammerer, CM Langefeld, CD Hayward, C Spracklen, CN Robinson-Cohen, C Hartman, CA Lindgren, CM Wang, C Sabanayagam, C Heng, C-K Lanzani, C Khor, C-C Cheng, C-Y Fuchsberger, C Gieger, C Shaffer, CM Schulz, C-A Willer, CJ Chasman, D Gudbjartsson, DF Ruggiero, D Toniolo, D Czamara, D Porteous, DJ Waterworth, DM Mascalzoni, D Mook-Kanamori, DO Reilly, DF Daw, EW Hofer, E Boerwinkle, E Salvi, E Bottinger, EP Tai, E-S Catamo, E Rizzi, F Guo, F Rivadeneira, F Guilianini, F Sveinbjornsson, G Ehret, G Waeber, G Biino, G Girotto, G Pistis, G Nadkarni, GN Delgado, GE Montgomery, GW Snieder, H Campbell, H White, HD Gao, H Stringham, HM Schmidt, H Li, H Brenner, H Holm, H Kirsten, H Kramer, H Rudan, I Nolte, IM Tzoulaki, I Olafsson, I Martins, J Cook, JP Wilson, JF Halbritter, J Felix, JF Divers, J Kooner, JS Lee, JJ-M O'Connell, J Rotter, J Liu, J Xu, J Thiery, J Arnlov, J Kuusisto, J Jakobsdottir, J Tremblay, J Chambers, JC Whitfield, JB Gaziano, JM Marten, J Coresh, J Jonas, JB Mychaleckyj, JC Christensen, K Eckardt, K-U Mohlke, KL Endlich, K Dittrich, K Ryan, KA Rice, KM Taylor, KD Ho, K Nikus, K Matsuda, K Strauch, K Miliku, K Hveem, K Lind, L Wallentin, L Yerges-Armstrong, LM Raffield, LM Phillips, LS Launer, LJ Lyytikainen, L-P Lange, LA Citterio, L Klaric, L Ikram, MA Ising, M Kleber, ME Francescatto, M Concas, MP Ciullo, M Piratsu, M Orho-Melander, M Laakso, M Loeffler, M Perola, M De Borst, MH Gogele, M La Bianca, M Lukas, MA Feitosa, MF Biggs, ML Wojczynski, MK Kavousi, M Kanai, M Akiyama, M Yasuda, M Nauck, M Waldenberger, M Chee, M-L Chee, M-L Boehnke, M Preuss, MH Stumvoll, M Province, MA Evans, MK O'Donoghue, ML Kubo, M Kahonen, M Kastarinen, M Nalls, MA Kuokkanen, M Ghanbari, M Bochud, M Josyula, NS Martin, NG Tan, NYQ Palmer, ND Pirastu, N Schupf, N Verweij, N Hutri-Kahonen, N Mononen, N Bansal, N Devuyst, O Melander, O Raitakari, OT Polasek, O Manunta, P Gasparini, P Mishra, PP Sulem, P Magnusson, PKE Elliott, P Ridker, PM Hamet, P Svensson, PO Joshi, PK Kovacs, P Pramstaller, PP Rossing, P Vollenweider, P Van der Harst, P Dorajoo, R Sim, RZH Burkhardt, R Tao, R Noordam, R Magi, R Schmidt, R De Mutsert, R Rueedi, R Van Dam, RM Carroll, RJ Gansevoort, RT Loos, RJF Felicita, SC Sedaghat, S Padmanabhan, S Freitag-Wolf, S Pendergrass, SA Graham, SE Gordon, SD Hwang, S-J Kerr, SM Vaccargiu, S Patil, SB Hallan, S Bakker, SJL Lim, S-C Lucae, S Vogelezang, S Bergmann, S Corre, T Ahluwalia, TS Lehtimaki, T Boutin, TS Meitinger, T Wong, T-Y Bergler, T Rabelink, TJ Esko, T Haller, T Thorsteinsdottir, U Voelker, U Foo, VHX Salomaa, V Vitart, V Giedraitis, V Gudnason, V Jaddoe, VWV Huang, W Zhang, W Wei, WB Kiess, W Marz, W Koenig, W Lieb, W Gao, X Sim, X Wang, YX Friedlander, Y Tham, Y-C Kamatani, Y Okada, Y Milaneschi, Y Yu, Z Stark, KJ Stefansson, K Boeger, CA Hung, AM Kronenberg, F Koettgen, A Pattaro, C Heid, IM
Item Type:	Journal Article
Abstract:	Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (nDM = 178,691, nnoDM = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM.
Issue Date:	13-Jun-2022
Date of Acceptance:	4-May-2022
URI:	http://hdl.handle.net/10044/1/97937
DOI:	10.1038/s42003-022-03448-z
ISSN:	2399-3642
Publisher:	Nature Research
Journal / Book Title:	Communications Biology
Volume:	5
Issue:	1
Copyright Statement:	Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/. © The Author(s) 2022
Sponsor/Funder:	Home Office Imperial College Healthcare NHS Trust- BRC Funding Medical Research Council (MRC) Medical Research Council (MRC) Medical Research Council (MRC) Medical Research Council (MRC) UK DRI Ltd
Funder's Grant Number:	7370192 RDF03 MR/S019669/1 MR/R023484/1 MR/L01632X/1 MR/L01632X/1 DRI-CORE2020-IMP
Keywords:	Science & Technology Life Sciences & Biomedicine Biology Multidisciplinary Sciences Life Sciences & Biomedicine - Other Topics Science & Technology - Other Topics GENOME-WIDE ASSOCIATION ENVIRONMENT INTERACTION QUALITY-CONTROL METAANALYSIS LOCI JOINT EFFICIENT SMOKING DISEASE EXPRESSION Lifelines cohort study DiscovEHR/MyCode study VA Million Veteran Program Kidney Humans Diabetic Nephropathies Diabetes Mellitus Creatinine Glomerular Filtration Rate Genome-Wide Association Study Science & Technology Life Sciences & Biomedicine Biology Multidisciplinary Sciences Life Sciences & Biomedicine - Other Topics Science & Technology - Other Topics GENOME-WIDE ASSOCIATION ENVIRONMENT INTERACTION QUALITY-CONTROL METAANALYSIS LOCI JOINT EFFICIENT SMOKING DISEASE EXPRESSION
Publication Status:	Published
Open Access location:	https://www.nature.com/articles/s42003-022-03448-z
Article Number:	ARTN 580
Online Publication Date:	2022-06-13
Appears in Collections:	School of Public Health

This item is licensed under a Creative Commons License