Genome-wide association and functional follow-up reveals new loci for kidney function.

Journal Article (Journal Article)

Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genome-wide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD.

Full Text

Duke Authors

Cited Authors

  • Pattaro, C; Köttgen, A; Teumer, A; Garnaas, M; Böger, CA; Fuchsberger, C; Olden, M; Chen, M-H; Tin, A; Taliun, D; Li, M; Gao, X; Gorski, M; Yang, Q; Hundertmark, C; Foster, MC; O'Seaghdha, CM; Glazer, N; Isaacs, A; Liu, C-T; Smith, AV; O'Connell, JR; Struchalin, M; Tanaka, T; Li, G; Johnson, AD; Gierman, HJ; Feitosa, M; Hwang, S-J; Atkinson, EJ; Lohman, K; Cornelis, MC; Johansson, Å; Tönjes, A; Dehghan, A; Chouraki, V; Holliday, EG; Sorice, R; Kutalik, Z; Lehtimäki, T; Esko, T; Deshmukh, H; Ulivi, S; Chu, AY; Murgia, F; Trompet, S; Imboden, M; Kollerits, B; Pistis, G; CARDIoGRAM Consortium, ; ICBP Consortium, ; CARe Consortium, ; Wellcome Trust Case Control Consortium 2 (WTCCC2), ; Harris, TB; Launer, LJ; Aspelund, T; Eiriksdottir, G; Mitchell, BD; Boerwinkle, E; Schmidt, H; Cavalieri, M; Rao, M; Hu, FB; Demirkan, A; Oostra, BA; de Andrade, M; Turner, ST; Ding, J; Andrews, JS; Freedman, BI; Koenig, W; Illig, T; Döring, A; Wichmann, H-E; Kolcic, I; Zemunik, T; Boban, M; Minelli, C; Wheeler, HE; Igl, W; Zaboli, G; Wild, SH; Wright, AF; Campbell, H; Ellinghaus, D; Nöthlings, U; Jacobs, G; Biffar, R; Endlich, K; Ernst, F; Homuth, G; Kroemer, HK; Nauck, M; Stracke, S; Völker, U; Völzke, H; Kovacs, P; Stumvoll, M; Mägi, R; Hofman, A; Uitterlinden, AG; Rivadeneira, F; Aulchenko, YS; Polasek, O; Hastie, N; Vitart, V; Helmer, C; Wang, JJ; Ruggiero, D; Bergmann, S; Kähönen, M; Viikari, J; Nikopensius, T; Province, M; Ketkar, S; Colhoun, H; Doney, A; Robino, A; Giulianini, F; Krämer, BK; Portas, L; Ford, I; Buckley, BM; Adam, M; Thun, G-A; Paulweber, B; Haun, M; Sala, C; Metzger, M; Mitchell, P; Ciullo, M; Kim, SK; Vollenweider, P; Raitakari, O; Metspalu, A; Palmer, C; Gasparini, P; Pirastu, M; Jukema, JW; Probst-Hensch, NM; Kronenberg, F; Toniolo, D; Gudnason, V; Shuldiner, AR; Coresh, J; Schmidt, R; Ferrucci, L; Siscovick, DS; van Duijn, CM; Borecki, I; Kardia, SLR; Liu, Y; Curhan, GC; Rudan, I; Gyllensten, U; Wilson, JF; Franke, A; Pramstaller, PP; Rettig, R; Prokopenko, I; Witteman, JCM; Hayward, C; Ridker, P; Parsa, A; Bochud, M; Heid, IM; Goessling, W; Chasman, DI; Kao, WHL; Fox, CS

Published Date

  • 2012

Published In

Volume / Issue

  • 8 / 3

Start / End Page

  • e1002584 -

PubMed ID

  • 22479191

Pubmed Central ID

  • PMC3315455

Electronic International Standard Serial Number (EISSN)

  • 1553-7404

Digital Object Identifier (DOI)

  • 10.1371/journal.pgen.1002584

Language

  • eng

Conference Location

  • United States