Genome-wide association and functional follow-up reveals new loci for kidney function.
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 None., ICBP Consortium None., CARe Consortium None., Wellcome Trust Case Control Consortium 2 (WTCCC2) None., 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.
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.