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ArTS Archivio della ricerca di Trieste
A large-scale GWAS provides insight on diabetes-dependent genetic effects on the glomerular filtration rate, a common metric to monitor kidney health in disease.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 (n(DM) = 178,691, n(noDM) = 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.
Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals
Winkler, Thomas W
;Rasheed, Humaira;Teumer, Alexander;Gorski, Mathias;Rowan, Bryce X;Stanzick, Kira J;Thomas, Laurent F;Tin, Adrienne;Hoppmann, Anselm;Chu, Audrey Y;Tayo, Bamidele;Thio, Chris H L;Cusi, Daniele;Chai, Jin-Fang;Sieber, Karsten B;Horn, Katrin;Li, Man;Scholz, Markus;Cocca, Massimiliano;Wuttke, Matthias;van der Most, Peter J;Yang, Qiong;Ghasemi, Sahar;Nutile, Teresa;Li, Yong;Pontali, Giulia;Günther, Felix;Dehghan, Abbas;Correa, Adolfo;Parsa, Afshin;Feresin, Agnese;de Vries, Aiko P J;Zonderman, Alan B;Smith, Albert V;Oldehinkel, Albertine J;De Grandi, Alessandro;Rosenkranz, Alexander R;Franke, Andre;Teren, Andrej;Metspalu, Andres;Hicks, Andrew A;Morris, Andrew P;Tönjes, Anke;Morgan, Anna;Podgornaia, Anna I;Peters, Annette;Körner, Antje;Mahajan, Anubha;Campbell, Archie;Freedman, Barry I;Spedicati, Beatrice;Ponte, Belen;Schöttker, Ben;Brumpton, Ben;Banas, Bernhard;Krämer, Bernhard K;Jung, Bettina;Åsvold, Bjørn Olav;Smith, Blair H;Ning, Boting;Penninx, Brenda W J H;Vanderwerff, Brett R;Psaty, Bruce M;Kammerer, Candace M;Langefeld, Carl D;Hayward, Caroline;Spracklen, Cassandra N;Robinson-Cohen, Cassianne;Hartman, Catharina A;Lindgren, Cecilia M;Wang, Chaolong;Sabanayagam, Charumathi;Heng, Chew-Kiat;Lanzani, Chiara;Khor, Chiea-Chuen;Cheng, Ching-Yu;Fuchsberger, Christian;Gieger, Christian;Shaffer, Christian M;Schulz, Christina-Alexandra;Willer, Cristen J;Chasman, Daniel I;Gudbjartsson, Daniel F;Ruggiero, Daniela;Toniolo, Daniela;Czamara, Darina;Porteous, David J;Waterworth, Dawn M;Mascalzoni, Deborah;Mook-Kanamori, Dennis O;Reilly, Dermot F;Daw, E Warwick;Hofer, Edith;Boerwinkle, Eric;Salvi, Erika;Bottinger, Erwin P;Tai, E-Shyong;Catamo, Eulalia;Rizzi, Federica;Guo, Feng;Rivadeneira, Fernando;Guilianini, Franco;Sveinbjornsson, Gardar;Ehret, Georg;Waeber, Gerard;Biino, Ginevra;Girotto, Giorgia;Pistis, Giorgio;Nadkarni, Girish N;Delgado, Graciela E;Montgomery, Grant W;Snieder, Harold;Campbell, Harry;White, Harvey D;Gao, He;Stringham, Heather M;Schmidt, Helena;Li, Hengtong;Brenner, Hermann;Holm, Hilma;Kirsten, Holgen;Kramer, Holly;Rudan, Igor;Nolte, Ilja M;Tzoulaki, Ioanna;Olafsson, Isleifur;Martins, Jade;Cook, James P;Wilson, James F;Halbritter, Jan;Felix, Janine F;Divers, Jasmin;Kooner, Jaspal S;Lee, Jeannette Jen-Mai;O'Connell, Jeffrey;Rotter, Jerome I;Liu, Jianjun;Xu, Jie;Thiery, Joachim;Ärnlöv, Johan;Kuusisto, Johanna;Jakobsdottir, Johanna;Tremblay, Johanne;Chambers, John C;Whitfield, John B;Gaziano, John M;Marten, Jonathan;Coresh, Josef;Jonas, Jost B;Mychaleckyj, Josyf C;Christensen, Kaare;Eckardt, Kai-Uwe;Mohlke, Karen L;Endlich, Karlhans;Dittrich, Katalin;Ryan, Kathleen A;Rice, Kenneth M;Taylor, Kent D;Ho, Kevin;Nikus, Kjell;Matsuda, Koichi;Strauch, Konstantin;Miliku, Kozeta;Hveem, Kristian;Lind, Lars;Wallentin, Lars;Yerges-Armstrong, Laura M;Raffield, Laura M;Phillips, Lawrence S;Launer, Lenore J;Lyytikäinen, Leo-Pekka;Lange, Leslie A;Citterio, Lorena;Klaric, Lucija;Ikram, M Arfan;Ising, Marcus;Kleber, Marcus E;Francescatto, Margherita;Concas, Maria Pina;Ciullo, Marina;Piratsu, Mario;Orho-Melander, Marju;Laakso, Markku;Loeffler, Markus;Perola, Markus;de Borst, Martin H;Gögele, Martin;Bianca, Martina La;Lukas, Mary Ann;Feitosa, Mary F;Biggs, Mary L;Wojczynski, Mary K;Kavousi, Maryam;Kanai, Masahiro;Akiyama, Masato;Yasuda, Masayuki;Nauck, Matthias;Waldenberger, Melanie;Chee, Miao-Li;Chee, Miao-Ling;Boehnke, Michael;Preuss, Michael H;Stumvoll, Michael;Province, Michael A;Evans, Michele K;O'Donoghue, Michelle L;Kubo, Michiaki;Kähönen, Mika;Kastarinen, Mika;Nalls, Mike A;Kuokkanen, Mikko;Ghanbari, Mohsen;Bochud, Murielle;Josyula, Navya Shilpa;Martin, Nicholas G;Tan, Nicholas Y Q;Palmer, Nicholette D;Pirastu, Nicola;Schupf, Nicole;Verweij, Niek;Hutri-Kähönen, Nina;Mononen, Nina;Bansal, Nisha;Devuyst, Olivier;Melander, Olle;Raitakari, Olli T;Polasek, Ozren;Manunta, Paolo;Gasparini, Paolo;Mishra, Pashupati P;Sulem, Patrick;Magnusson, Patrik K E;Elliott, Paul;Ridker, Paul M;Hamet, Pavel;Svensson, Per O;Joshi, Peter K;Kovacs, Peter;Pramstaller, Peter P;Rossing, Peter;Vollenweider, Peter;van der Harst, Pim;Dorajoo, Rajkumar;Sim, Ralene Z H;Burkhardt, Ralph;Tao, Ran;Noordam, Raymond;Mägi, Reedik;Schmidt, Reinhold;de Mutsert, Renée;Rueedi, Rico;van Dam, Rob M;Carroll, Robert J;Gansevoort, Ron T;Loos, Ruth J F;Felicita, Sala Cinzia;Sedaghat, Sanaz;Padmanabhan, Sandosh;Freitag-Wolf, Sandra;Pendergrass, Sarah A;Graham, Sarah E;Gordon, Scott D;Hwang, Shih-Jen;Kerr, Shona M;Vaccargiu, Simona;Patil, Snehal B;Hallan, Stein;Bakker, Stephan J L;Lim, Su-Chi;Lucae, Susanne;Vogelezang, Suzanne;Bergmann, Sven;Corre, Tanguy;Ahluwalia, Tarunveer S;Lehtimäki, Terho;Boutin, Thibaud S;Meitinger, Thomas;Wong, Tien-Yin;Bergler, Tobias;Rabelink, Ton J;Esko, Tõnu;Haller, Toomas;Thorsteinsdottir, Unnur;Völker, Uwe;Foo, Valencia Hui Xian;Salomaa, Veikko;Vitart, Veronique;Giedraitis, Vilmantas;Gudnason, Vilmundur;Jaddoe, Vincent W V;Huang, Wei;Zhang, Weihua;Wei, Wen Bin;Kiess, Wieland;März, Winfried;Koenig, Wolfgang;Lieb, Wolfgang;Gao, Xin;Sim, Xueling;Wang, Ya Xing;Friedlander, Yechiel;Tham, Yih-Chung;Kamatani, Yoichiro;Okada, Yukinori;Milaneschi, Yuri;Yu, Zhi;Stark, Klaus J;Stefansson, Kari;Böger, Carsten A;Hung, Adriana M;Kronenberg, Florian;Köttgen, Anna;Pattaro, Cristian;Heid, Iris M
2022
Abstract
A large-scale GWAS provides insight on diabetes-dependent genetic effects on the glomerular filtration rate, a common metric to monitor kidney health in disease.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 (n(DM) = 178,691, n(noDM) = 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.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11368/3025486
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simulazione ASN
Il report seguente simula gli indicatori relativi alla propria produzione scientifica in relazione alle soglie ASN 2021-2023 del proprio SC/SSD. Si ricorda che il superamento dei valori soglia (almeno 2 su 3) è requisito necessario ma non sufficiente al conseguimento dell'abilitazione. La simulazione si basa sui dati IRIS e sugli indicatori bibliometrici alla data indicata e non tiene conto di eventuali periodi di congedo obbligatorio, che in sede di domanda ASN danno diritto a incrementi percentuali dei valori. La simulazione può differire dall'esito di un’eventuale domanda ASN sia per errori di catalogazione e/o dati mancanti in IRIS, sia per la variabilità dei dati bibliometrici nel tempo. Si consideri che Anvur calcola i valori degli indicatori all'ultima data utile per la presentazione delle domande.
La presente simulazione è stata realizzata sulla base delle specifiche raccolte sul tavolo ER del Focus Group IRIS coordinato dall’Università di Modena e Reggio Emilia e delle regole riportate nel DM 589/2018 e allegata Tabella A. Cineca, l’Università di Modena e Reggio Emilia e il Focus Group IRIS non si assumono alcuna responsabilità in merito all’uso che il diretto interessato o terzi faranno della simulazione. Si specifica inoltre che la simulazione contiene calcoli effettuati con dati e algoritmi di pubblico dominio e deve quindi essere considerata come un mero ausilio al calcolo svolgibile manualmente o con strumenti equivalenti.