Meta-analysis identifies multiple loci associated with kidney function–related traits in east Asian populations

Okada, Yukinori; Sim, Xueling; Min Jin Go,; Jer-Yuarn, Wu; Dongfeng, Gu; Takeuchi, Fumihiko; Takahashi, Atsushi; Maeda, Shiro; Tsunoda, Tatsuhiko; Chen, Peng; Lim, Su-Chi; Wong, Tien-Yin; Liu, Jianjun; Young, Terri L.; Aung, Tin; Seielstad, Mark; Teo, Yik-Ying; Young Jin Kim,; Lee, Jong-Young; Han, Bok-Ghee; Kang, Daehee; Chen, Chien-Hsiun; Tsai, Fuu-Jen; Chang, Li-Ching; Cathy Fann, S. -J.; Mei, Hao; Rao, Dabeeru C.; Hixson, James E.; Chen, Shufeng; Katsuya, Tomohiro; Isono, Masato; Ogihara, Toshio; Chambers, John C.; Zhang, Weihua; Kooner, Jaspal S.; the KidneyGen consortium,; the CKDGen consortium,; Albrecht, Eva; the GUGC consortium,; Yamamoto, Kazuhiko; Kubo, Michiaki; Nakamura, Yusuke; Kamatani, Naoyuki; Kato, Norihiro; Jiang, He; Chen, Yuan-Tsong; Yoon Shin Cho,; Tai, E-Shyong; Tanaka, Toshihiro; John, C Chambers; Zhang, Weihua; Graham, M Lord–; Pim van der Harst,; Debbie, A Lawlor; Joban, S Sehmi; Daniel, P Gale; Mark, N Wass; Kourosh, R Ahmadi; Stephan J, L Bakker; Beckmann, Jacqui; Henk J, G Bilo; Bochud, Murielle; Morris, J Brown; Mark, J Caulfield; John M, C Connell; H Terence Cook,; Cotlarciuc, Ioana; George Davey Smith,; Ranil de Silva,; Deng, Guohong; Devuyst, Olivier; Lambert, D Dikkeschei; Dimkovic, Nada; Dockrell, Mark; Dominiczak, Anna; Ebrahim, Shah; Eggermann, Thomas; Farrall, Martin; Ferrucci, Luigi; Floege, Jurgen; Nita, G Forouhi; Ron, T Gansevoort; Han, Xijin; Hedblad, Bo; Jaap, J Homan van der Heide; Bouke, G Hepkema; Hernandez-Fuentes–, Maria; Hypponen, Elina; Johnson, Toby; Paul, E de Jong; Kleefstra, Nanne; Lagou, Vasiliki; Lapsley, Marta; Yun, Li; Ruth J, F Loos; Luan, Jian’An; Luttropp, Karin; Maréchal, Céline; Melander, Olle; Patricia, B Munroe; Nordfors, Louise; Parsa, Afshin; Peltonen–, Leena; Brenda, W Penninx–; Perucha–, Esperanza; Pouta, Anneli; Prokopenko–, Inga; Paul, J Roderick; Ruokonen, Aimo; Nilesh, J Samani; Sanna, Serena; Schalling, Martin; Schlessinger, David; Schlieper, Georg; Marc A, J Seelen; Alan, R Shuldiner; Sjögren, Marketa; Johannes, H Smit–; Snieder, Harold; Soranzo, Nicole; Timothy, D Spector; Stenvinkel, Peter; Michael J, E Sternberg; Swaminathan, Ramasamyiyer; Tanaka, Toshiko; Lielith, J Ubink-Veltmaat; Uda, Manuela; Vollenweider, Peter; Wallace, Chris; Waterworth, Dawn; Zerres, Klaus; Waeber, Gerard; Nicholas, J Wareham; Patrick, H Maxwell; Mark, I McCarthy–; Jarvelin, Marjo-Riitta; Mooser, Vincent; Goncalo, R Abecasis; Lightstone, Liz; Scott, James; Navis, Gerjan; Elliott, Paul; &amp;,; Jaspal, S Kooner; Köttgen, Anna; Pattaro, Cristian; Carsten, A Böger; Fuchsberger, Christian; Olden, Matthias; Nicole, L Glazer; Parsa, Afshin; Gao, Xiaoyi; Yang, Qiong; Albert, V Smith; Jeffrey, R O’Connell; Man, Li; Schmidt, Helena; Tanaka, Toshiko; Isaacs, Aaron; Ketkar, Shamika; Hwang, Shih-Jen; Andrew, D Johnson; Dehghan, Abbas; Teumer, Alexander; Paré, Guillaume; Elizabeth, J Atkinson; Zeller, Tanja; Lohman, Kurt; Marilyn, C Cornelis; Nicole, M Probst-Hensch; Kronenberg, Florian; Tönjes, Anke; Hayward, Caroline; Aspelund, Thor; Eiriksdottir, Gudny; Lenore, J Launer; Tamara, B Harris; Rampersaud, Evadnie; Braxton, D Mitchell; Dan, E Arking; Boerwinkle, Eric; Struchalin, Maksim; Cavalieri, Margherita; Singleton, Andrew; Giallauria, Francesco; Metter, Jeffrey; Ian, H de Boer; Haritunians, Talin; Lumley, Thomas; Siscovick, David; Bruce, M Psaty–; M Carola Zillikens,; Ben, A Oostra; Feitosa, Mary; Province, Michael; Mariza de Andrade,; Stephen, T Turner; Schillert, Arne; Ziegler, Andreas; Philipp, S Wild; Renate, B Schnabel; Wilde, Sandra; Thomas, F Munzel; Tennille, S Leak; Illig, Thomas; Klopp, Norman; Meisinger, Christa; Wichmann–, H-Erich; Koenig, Wolfgang; Zgaga, Lina; Zemunik, Tatijana; Kolcic, Ivana; Minelli, Cosetta; Frank, B Hu; Johansson, Åsa; Igl, Wilmar; Zaboli, Ghazal; Sarah, H Wild; Alan, F Wright; Campbell, Harry; Ellinghaus, David; Schreiber, Stefan; Yurii, S Aulchenko; Janine, F Felix; Rivadeneira, Fernando; Andre, G Uitterlinden; Hofman, Albert; Imboden, Medea; Nitsch, Dorothea; Brandstätter, Anita; Kollerits, Barbara; Kedenko, Lyudmyla; Mägi, Reedik; Stumvoll, Michael; Kovacs, Peter; Boban, Mladen; Campbell, Susan; Endlich, Karlhans; Völzke, Henry; Heyo, K Kroemer; Nauck, Matthias; Völker, Uwe; Polasek, Ozren; Vitart, Veronique; Badola, Sunita; Alexander, N Parker; Paul, M Ridker; Sharon L, R Kardia; Blankenberg, Stefan; Liu, Yongmei; Gary, C Curhan; Franke, Andre; Rochat, Thierry; Paulweber, Bernhard; Prokopenko, Inga; Wang, Wei; Gudnason, Vilmundur; Alan, R Shuldiner; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; Michael, G Shlipak; Cornelia, M van Duijn; Borecki, Ingrid; Bernhard, K Krämer; Rudan, Igor; Gyllensten, Ulf; James, F Wilson; Jacqueline, C Witteman; Peter, P Pramstaller; Rettig, Rainer; Hastie, Nick; Daniel, I Chasman; H Kao, W; Iris, M Heid; &amp;,; Caroline, S Fox; Köttgen, Anna; Albrecht, Eva; Teumer, Alexander; Vitart, Veronique; Krumsiek, Jan; Hundertmark, Claudia; Pistis, Giorgio; Ruggiero, Daniela; Conall, M O’Seaghdha; Haller, Toomas; Yang, Qiong; Tanaka, Toshiko; Andrew, D Johnson; Kutalik, Zoltán; Albert, V Smith; Shi, Julia; Struchalin, Maksim; Rita PS Middelberg,; Morris, J Brown; Angelo, L Gaffo; Pirastu, Nicola; Guo, Li; Hayward, Caroline; Zemunik, Tatijana; Huffman, Jennifer; Yengo, Loic; Jing Hua Zhao,; Demirkan, Ayse; Mary, F Feitosa; Liu, Xuan; Malerba, Giovanni; Lorna, M Lopez; Pim van der Harst,; Xinzhong, Li; Marcus, E Kleber; Andrew, A Hicks; Ilja, M Nolte; Johansson, Asa; Murgia, Federico; Sarah, H Wild; Stephan JL Bakker,; John, F Peden; Dehghan, Abbas; Steri, Maristella; Tenesa, Albert; Lagou, Vasiliki; Salo, Perttu; Mangino, Massimo; Lynda, M Rose; Lehtimäki, Terho; Owen, M Woodward; Okada, Yukinori; Tin, Adrienne; Müller, Christian; Oldmeadow, Christopher; Putku, Margus; Czamara, Darina; Kraft, Peter; Frogheri, Laura; Gian Andri Thun,; Grotevendt, Anne; Gauti Kjartan Gislason,; Tamara, B Harris; Lenore, J Launer; Mcardle, Patrick; Alan, R Shuldiner; Boerwinkle, Eric; Coresh, Josef; Schmidt, Helena; Schallert, Michael; Nicholas, G Martin; Grant, W Montgomery; Kubo, Michiaki; Nakamura, Yusuke; Tanaka, Toshihiro; Patricia, B Munroe; Nilesh, J Samani; David, R Jacobs Jr; Liu, Kiang; D'Adamo, Pio; Ulivi, Sheila; Jerome, I Rotter; Bruce, M Psaty; Vollenweider, Peter; Waeber, Gerard; Campbell, Susan; Devuyst, Olivier; Navaro, Pau; Kolcic, Ivana; Hastie, Nicholas; Balkau, Beverley; Froguel, Philippe; Esko, Tõnu; Salumets, Andres; Kay Tee Khaw,; Langenberg, Claudia; Nicholas, J Wareham; Isaacs, Aaron; Kraja, Aldi; Zhang, Qunyuan; Philipp, S Wild; Rodney, J Scott; Elizabeth, G Holliday; Org, Elin; Viigimaa, Margus; Bandinelli, Stefania; Jeffrey, E Metter; Lupo, Antonio; Trabetti, Elisabetta; Sorice, Rossella; Döring, Angela; Lattka, Eva; Strauch, Konstantin; Theis, Fabian; Waldenberger, Melanie; Wichmann, H-Erich; Davies, Gail; Alan, J Gow; Bruinenberg, Marcel; LifeLines Cohort Study,; Ronald, P Stolk; Jaspal, S Kooner; Zhang, Weihua; Bernhard, R Winkelmann; Bernhard, O Boehm; Lucae, Susanne; Brenda, W Penninx-; Johannes, H Smit; Curhan, Gary; Mudgal, Poorva; Robert, M Plenge; Portas, Laura; Persico, Ivana; Kirin, Mirna; James, F Wilson; Irene Mateo Leach,; Wiek, H van Gilst; Goel, Anuj; Ongen, Halit; Hofman, Albert; Rivadeneira, Fernando; Andre, G Uitterlinden; Imboden, Medea; Arnold von Eckardstein,; Cucca, Francesco; Nagaraja, Ramaiah; Piras, MARIA GRAZIA; Nauck, Matthias; Schurmann, Claudia; Budde, Kathrin; Ernst, Florian; Susan, M Farrington; Theodoratou, Evropi; Prokopenko, Inga; Stumvoll, Michael; Jula, Antti; Perola, Markus; Salomaa, Veikko; Shin, So-Youn; Tim, D Spector; Sala, Cinzia; Paul, M Ridker; Kähönen, Mika; Viikari, Jorma; Hengstenberg, Christian; Christopher, P Nelson; the CARDIoGRAM Consortium,; the DIAGRAM Consortium,; the ICBP Consortium,; the MAGIC Consortium,; James, F Meschia; Michael, A Nalls; Sharma, Pankaj; Andrew, B Singleton; Kamatani, Naoyuki; Zeller, Tanja; Burnier, Michel; Attia, John; Laan, Maris; Klopp, Norman; Hans, L Hillege; Kloiber, Stefan; Choi, Hyon; Pirastu, Mario; Tore, Silvia; Nicole, M Probst-Hensch; Völzke, Henry; Gudnason, Vilmundur; Parsa, Afshin; Schmidt, Reinhold; John, B Whitfield; Fornage, Myriam; Gasparini, Paolo; David, S Siscovick; Polasek, Ozren; Campbell, Harry; Rudan, Igor; Bouatia-Naji, Nabila; Metspalu, Andres; Ruth JF Loos,; Cornelia, M van Duijn; Ingrid, B Borecki; Ferrucci, Luigi; Gambaro, Giovanni; Ian, J Deary; Bruce HR Wolffenbuttel,; John, C Chambers; März, Winfried; Peter, P Pramstaller; Snieder, Harold; Gyllensten, Ulf; Alan, F Wright; Navis, Gerjan; Hugh Watkins on behalf of PROCARDIS,; Jacqueline CM Witteman,; Sanna, Serena; Schipf, Sabine; Malcolm, G Dunlop; Tönjes, Anke; Ripatti, Samuli; Soranzo, Nicole; Toniolo, Daniela; Daniel, I Chasman; Raitakari, Olli; WH Linda Kao,; Ciullo, Marina; Caroline, S Fox; Caulfield, Mark; Bochud, Murielle; Gieger, Christian

doi:10.1038/ng.2352

Chronic kidney disease (CKD), impairment of kidney function, is a serious public health problem, and the assessment of genetic factors influencing kidney function has substantial clinical relevance. Here, we report a meta-analysis of genome-wide association studies for kidney function-related traits, including 71,149 east Asian individuals from 18 studies in 11 population-, hospital-or family-based cohorts, conducted as part of the Asian Genetic Epidemiology Network (AGEN). Our meta-analysis identified 17 loci newly associated with kidney function-related traits, including the concentrations of blood urea nitrogen, uric acid and serum creatinine and estimated glomerular filtration rate based on serum creatinine levels (eGFRcrea) (P < 5.0 × 10-8). We further examined these loci with in silico replication in individuals of European ancestry from the KidneyGen, CKDGen and GUGC consortia, including a combined total of ∼110,347 individuals. We identify pleiotropic associations among these loci with kidney function-related traits and risk of CKD. These findings provide new insights into the genetics of kidney function. © 2012 Nature America, Inc. All rights reserved.