A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä

Genome-Wide Association and Functional Follow-Up Reveals New Loci for Kidney Function




TekijätPattaro C, Kottgen A, Teumer A, Garnaas M, Boger CA, Fuchsberger C, Olden M, Chen MH, Tin A, Taliun D, Li M, Gao XY, Gorski M, Yang Q, Hundertmark C, Foster MC, O'Seaghdha CM, Glazer N, Isaacs A, Liu CT, Smith AV, O'Connell JR, Struchalin M, Tanaka T, Li G, Johnson AD, Gierman HJ, Feitosa M, Hwang SJ, Atkinson EJ, Lohman K, Cornelis MC, Johansson A, Tonjes A, Dehghan A, Chouraki V, Holliday EG, Sorice R, Kutalik Z, Lehtimaki T, Esko T, Deshmukh H, Ulivi S, Chu AY, Murgia F, Trompet S, Imboden M, Kollerits B, Pistis G, 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 JZ, Andrews JS, Freedman BI, Koenig W, Illig T, Doring A, Wichmann HE, Kolcic I, Zemunik T, Boban M, Minelli C, Wheeler HE, Igl W, Zaboli G, Wild SH, Wright AF, Campbell H, Ellinghaus D, Nothlings U, Jacobs G, Biffar R, Endlich K, Ernst F, Homuth G, Kroemer HK, Nauck M, Stracke S, Volker U, Volzke H, Kovacs P, Stumvoll M, Magi R, Hofman A, Uitterlinden AG, Rivadeneira F, Aulchenko YS, Polasek O, Hastie N, Vitart V, Helmer C, Wang JJ, Ruggiero D, Bergmann S, Kahonen M, Viikari J, Nikopensius T, Province M, Ketkar S, Colhoun H, Doney A, Robino A, Giulianini F, Kramer BK, Portas L, Ford I, Buckley BM, Adam M, Thun GA, 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 YM, 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

KustantajaPUBLIC LIBRARY SCIENCE

Julkaisuvuosi2012

JournalPLoS Genetics

Tietokannassa oleva lehden nimiPLOS GENETICS

Lehden akronyymiPLOS GENET

Artikkelin numeroARTN e1002584

Numero sarjassa3

Vuosikerta8

Numero3

Sivujen määrä15

ISSN1553-7390

DOIhttps://doi.org/10.1371/journal.pgen.1002584


Tiivistelmä
Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genomewide 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.



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