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

Okada, Y; Sim, X; Mj, Go; Jy, Wu; D, Gu; Takeuchi, F; Takahashi, A; Maeda, S; Tsunoda, T; Chen, P; Lim, Sc; Wong, Ty; Liu, J; Young, Tl; Aung, T; Seielstad, M; Teo, Yy; Kim, Yj; Lee, Jy; Han, Bg; Kang, D; Chen, Ch; Tsai, Fj; Chang, Lc; Fann, Sj; Mei, H; Rao, Dc; Hixson, Je; Chen, S; Katsuya, T; Isono, M; Ogihara, T; Chambers, Jc; Zhang, W; Kooner, Js; Consortium, Kidneygen; Consortium, Ckdgen; Albrecht, E; Consortium, Gugc; Yamamoto, K; Kubo, M; Nakamura, Y; Kamatani, N; Kato, N; J, He; Chen, Yt; Cho, Ys; Tai, Es; Tanaka, T.; Chambers, Jc; Zhang, W; Lord, Gm; van der Harst, P; Lawlor, Da; Sehmi, Js; Gale, Dp; Wass, Mn; Ahmadi, Kr; Bakker, Sj; Beckmann, J; Bilo, Hj; Bochud, M; Brown, Mj; Caulfield, Mj; Connell, Jm; Cook, Ht; Cotlarciuc, I; Smith, Gd; de Silva, R; Deng, G; Devuyst, O; Dikkeschei, Ld; Dimkovic, N; Dockrell, M; Dominiczak, A; Ebrahim, S; Eggermann, T; Farrall, M; Ferrucci, L; Floege, J; Forouhi, Ng; Gansevoort, Rt; Han, X; Hedblad, B; van der Heide JJ,; Hepkema, Bg; Hernandez Fuentes, M; Hypponen, E; Johnson, T; de Jong PE,; Kleefstra, N; Lagou, V; Lapsley, M; Y, Li; Loos, Rj; Luan, J; Luttropp, K; Maréchal, C; Melander, O; Munroe, Pb; Nordfors, L; Parsa, A; Peltonen, L; Penninx, Bw; Perucha, E; Pouta, A; Prokopenko, I; Roderick, Pj; Ruokonen, A; Samani, Nj; Sanna, S; Schalling, M; Schlessinger, D; Schlieper, G; Seelen, Ma; Shuldiner, Ar; Sjögren, M; Smit, Jh; Snieder, H; Soranzo, N; Spector, Td; Stenvinkel, P; Sternberg, Mj; Swaminathan, R; Tanaka, T; Ubink Veltmaat LJ,; Uda, M; Vollenweider, P; Wallace, C; Waterworth, D; Zerres, K; Waeber, G; Wareham, Nj; Maxwell, Ph; Mccarthy, Mi; Jarvelin, Mr; Mooser, V; Abecasis, Gr; Lightstone, L; Scott, J; Navis, G; Elliott, P; Kooner, Js; Köttgen, A; Pattaro, C; Böger, Ca; Fuchsberger, C; Olden, M; Glazer, Nl; Parsa, A; Gao, X; Yang, Q; Smith, Av; O'Connell, Jr; M, Li; Schmidt, H; Tanaka, T; Isaacs, A; Ketkar, S; Hwang, Sj; Johnson, Ad; Dehghan, A; Teumer, A; Paré, G; Atkinson, Ej; Zeller, T; Lohman, K; Cornelis, Mc; Probst Hensch NM,; Kronenberg, F; Tönjes, A; Hayward, C; Aspelund, T; Eiriksdottir, G; Launer, Lj; Harris, Tb; Rampersaud, E; Mitchell, Bd; Arking, De; Boerwinkle, E; Struchalin, M; Cavalieri, M; Singleton, A; Giallauria, F; Metter, J; de Boer IH,; Haritunians, T; Lumley, T; Siscovick, D; Psaty, Bm; Zillikens, Mc; Oostra, Ba; Feitosa, M; Province, M; de Andrade, M; Turner, St; Schillert, A; Ziegler, A; Wild, Ps; Schnabel, Rb; Wilde, S; Munzel, Tf; Leak, Ts; Illig, T; Klopp, N; Meisinger, C; Wichmann, He; Koenig, W; Zgaga, L; Zemunik, T; Kolcic, I; Minelli, C; Fb, Hu; Johansson, Å; Igl, W; Zaboli, G; Wild, Sh; Wright, Af; Campbell, H; Ellinghaus, D; Schreiber, S; Aulchenko, Ys; Felix, Jf; Rivadeneira, F; Uitterlinden, Ag; Hofman, A; Imboden, M; Nitsch, D; Brandstätter, A; Kollerits, B; Kedenko, L; Mägi, R; Stumvoll, M; Kovacs, P; Boban, M; Campbell, S; Endlich, K; Völzke, H; Kroemer, Hk; Nauck, M; Völker, U; Polasek, O; Vitart, V; Badola, S; Parker, An; Ridker, Pm; Kardia, Sl; Blankenberg, S; Liu, Y; Curhan, Gc; Franke, A; Rochat, T; Paulweber, B; Prokopenko, I; Wang, W; Gudnason, V; Shuldiner, Ar; Coresh, J; Schmidt, R; Ferrucci, L; Shlipak, Mg; van Duijn CM,; Borecki, I; Krämer, Bk; Rudan, I; Gyllensten, U; Wilson, Jf; Witteman, Jc; Pramstaller, Pp; Rettig, R; Hastie, N; Chasman, Di; Kao, Wh; Heid, Im; Fox, Cs; Köttgen, A; Albrecht, E; Teumer, A; Vitart, V; Krumsiek, J; Hundertmark, C; Pistis, G; Ruggiero, D; O'Seaghdha, M; Haller, T; Yang, Q; Tanaka, T; Johnson, Ad; Kutalik, Z; Smith, Av; Shi, J; Struchalin, M; Middelberg, Ps; Brown, Mj; Gaffo, Al; Pirastu, N; G, Li; Hayward, C; Zemunik, T; Huffman, J; Yengo, L; Zhao, Jh; Demirkan, A; Feitosa, Mf; Liu, X; Malerba, Giovanni; Lopez, Lm; van der Harst, P; X, Li; Kleber, Me; Hicks, Aa; Nolte, Im; Johansson, A; Murgia, F; Wild, Sh; Bakker, Sj; Peden, Jf; Dehghan, A; Steri, M; Tenesa, A; Lagou, V; Salo, P; Mangino, M; Rose, Lm; Lehtimäki, T; Woodward, Om; Okada, Y; Tin, A; Müller, C; Oldmeadow, C; Putku, M; Czamara, D; Kraft, P; Frogheri, L; Thun, Ga; Grotevendt, A; Gislason, Gk; Harris, Tb; Launer, Lj; Mcardle, P; Shuldiner, Ar; Boerwinkle, E; Coresh, J; Schmidt, H; Schallert, M; Martin, Ng; Montgomery, Gw; Kubo, M; Nakamura, Y; Tanaka, T; Munroe, Pb; Samani, Nj; Jacobs DR Jr,; Liu, K; D'Adamo, P; Ulivi, S; Rotter, Ji; Psaty, Bm; Vollenweider, P; Waeber, G; Campbell, S; Devuyst, O; Navaro, P; Kolcic, I; Hastie, N; Balkau, B; Froguel, P; Esko, T; Salumets, A; Khaw, Kt; Langenberg, C; Wareham, Nj; Isaacs, A; Kraja, A; Zhang, Q; Wild, Ps; Scott, Rj; Holliday, Eg; Org, E; Viigimaa, M; Bandinelli, S; Metter, Je; Lupo, Antonio; Trabetti, Elisabetta; Sorice, R; Döring, A; Lattka, E; Strauch, K; Theis, F; Waldenberger, M; Wichmann, He; Davies, G; Gow, Aj; Bruinenberg, M; Stolk, Rp; Kooner, Js; Zhang, W; Winkelmann, Br; Boehm, Bo; Lucae, S; Penninx, Bw; Smit, Jh; Curhan, G; Mudgal, P; Plenge, Rm; Portas, L; Persico, I; Kirin, M; Wilson, Jf; Mateo Leach, I; van Gilst WH,; Goel, A; Ongen, H; Hofman, A; Rivadeneira, F; Uitterlinden, Ag; Imboden, M; von Eckardstein, A; Cucca, F; Nagaraja, R; Piras, Mg; Nauck, M; Schurmann, C; Budde, K; Ernst, F; Farrington, Sm; Theodoratou, E; Prokopenko, I; Stumvoll, M; Jula, A; Perola, M; Salomaa, V; Shin, Sy; Spector, Td; Sala, C; Ridker, Pm; Kähönen, M; Viikari, J; Hengstenberg, C; Nelson, Cp; Meschia, Jf; Nalls, Ma; Sharma, P; Singleton, Ab; Kamatani, N; Zeller, T; Burnier, M; Attia, J; Laan, M; Klopp, N; Hillege, Hl; Kloiber, S; Choi, H; Pirastu, M; Tore, S; Probst Hensch NM,; Völzke, H; Gudnason, V; Parsa, A; Schmidt, R; Whitfield, Jb; Fornage, M; Gasparini, P; Siscovick, Ds; Polasek, O; Campbell, H; Rudan, I; Bouatia Naji, N; Metspalu, A; Loos, Rj; van Duijn CM,; Borecki, Ib; Ferrucci, L; Gambaro, G; Deary, Ij; Wolffenbuttel, Bh; Chambers, Jc; März, W; Pramstaller, Pp; Snieder, H; Gyllensten, U; Wright, Af; Navis, G; Watkins, H; Witteman, Jc; Sanna, S; Schipf, S; Dunlop, Mg; Tönjes, A; Ripatti, S; Soranzo, N; Toniolo, D; Chasman, Di; Raitakari, O; Kao, Wh; Ciullo, M; Fox, Cs; Caulfield, M; Bochud, M; Gieger, C.

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.