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

Tuesday,2012-11-06 12:26 America/Los_Angeles — eenright
TitleGenome-wide association and functional follow-up reveals new loci for kidney function.
Publication TypeJournal Article
Year of Publication2012
AuthorsPattaro, 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, A, 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, 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, JJin, 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, J Jukema, W, 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, LWH, Fox, CS
Corporate/Institutional AuthorsCARDIoGRAM consortium, ICBP Consortium,, CARe Consortium,, Wellcome Trust Case Control Consortium 2 (WTCCC2),
JournalPLoS Genet
Volume8
Issue3
Paginatione1002584
Date Published2012
ISSN1553-7404
KeywordsAfrican Americans, Aged, Animals, Caspase 9, Cyclin-Dependent Kinases, DEAD-box RNA Helicases, DNA Helicases, European Continental Ancestry Group, Female, Follow-Up Studies, Gene Knockdown Techniques, Genome-Wide Association Study, Glomerular Filtration Rate, Humans, Kidney, Kidney Failure, Chronic, Male, Middle Aged, Phosphoric Diester Hydrolases, Zebrafish
Abstract<p>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.</p>
DOI10.1371/journal.pgen.1002584
Alternate JournalPLoS Genet.
PubMed ID22479191
PubMed Central IDPMC3315455
Grant ListHHSN268201100012C / HL / NHLBI NIH HHS / United States
U01HG004446 / HG / NHGRI NIH HHS / United States
UL1RR025005 / RR / NCRR NIH HHS / United States
N02-HL-6-4278 / HL / NHLBI NIH HHS / United States
N01-HC-25195 / HC / NHLBI NIH HHS / United States
CZB/4/710 / / Chief Scientist Office / United Kingdom
HHSN268201100009I / HL / NHLBI NIH HHS / United States
U01HG004726 / HG / NHGRI NIH HHS / United States
U01HG004438 / HG / NHGRI NIH HHS / United States
5R01HL08770002 / HL / NHLBI NIH HHS / United States
R01 DK058845 / DK / NIDDK NIH HHS / United States
K12 RR023250 / RR / NCRR NIH HHS / United States
U01 HG004728 / HG / NHGRI NIH HHS / United States
U01 HG004438 / HG / NHGRI NIH HHS / United States
P01CA087969 / CA / NCI NIH HHS / United States
U01 HG004446 / HG / NHGRI NIH HHS / United States
N01-HC-85085 / HC / NHLBI NIH HHS / United States
R01HL59367 / HL / NHLBI NIH HHS / United States
HHSN268201100010C / HL / NHLBI NIH HHS / United States
UL1 RR025005 / RR / NCRR NIH HHS / United States
N01 AG062101 / AG / NIA NIH HHS / United States
U01HG004738 / HG / NHGRI NIH HHS / United States
P01 CA087969 / CA / NCI NIH HHS / United States
HHSN268201100008C / HL / NHLBI NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
HL 043851 / HL / NHLBI NIH HHS / United States
P01CA055075 / CA / NCI NIH HHS / United States
HHSN268201100005G / HL / NHLBI NIH HHS / United States
HL69757 / HL / NHLBI NIH HHS / United States
HHSN268201100008I / HL / NHLBI NIH HHS / United States
K12RR023250 / RR / NCRR NIH HHS / United States
N01-HC-85081 / HC / NHLBI NIH HHS / United States
U01HG004415 / HG / NHGRI NIH HHS / United States
HHSN268201100005C / / PHS HHS / United States
R01 HL043851 / HL / NHLBI NIH HHS / United States
U01 DE018993 / DE / NIDCR NIH HHS / United States
R01 HL059367 / HL / NHLBI NIH HHS / United States
U01HG004735 / HG / NHGRI NIH HHS / United States
R01 HL087660 / HL / NHLBI NIH HHS / United States
HHSN268201100007C / HL / NHLBI NIH HHS / United States
P01 CA055075 / CA / NCI NIH HHS / United States
MC_U127561128 / / Medical Research Council / United Kingdom
N01 HC015103 / HC / NHLBI NIH HHS / United States
085475/08/Z / / Wellcome Trust / United Kingdom
HHSN268201100009C / / PHS HHS / United States
/ / Medical Research Council / United Kingdom
T32 HL007575 / HL / NHLBI NIH HHS / United States
HHSN268201100011I / HL / NHLBI NIH HHS / United States
HHSN268201100011C / HL / NHLBI NIH HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
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1R01AG032098-01A1 / AG / NIA NIH HHS / United States
U01 GM074518-04 / GM / NIGMS NIH HHS / United States
R01 HL087652 / HL / NHLBI NIH HHS / United States
HHSN268200625226C / / PHS HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
U01 HG004424 / HG / NHGRI NIH HHS / United States
R01 DK075787 / DK / NIDDK NIH HHS / United States
N01-AG-1-2100 / AG / NIA NIH HHS / United States
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U01HG004399 / HG / NHGRI NIH HHS / United States
N01 AG062106 / AG / NIA NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
R01 AG025941 / AG / NIA NIH HHS / United States
N01-HC-85086 / HC / NHLBI NIH HHS / United States
U01 HG004415 / HG / NHGRI NIH HHS / United States
HHSN268201100010C / / PHS HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
U01HG004402 / HG / NHGRI NIH HHS / United States
U01HG004422 / HG / NHGRI NIH HHS / United States
DK66574 / DK / NIDDK NIH HHS / United States
CA 047988 / CA / NCI NIH HHS / United States
R01 AG032098 / AG / NIA NIH HHS / United States
U01 HL084756 / HL / NHLBI NIH HHS / United States
N01-HC-85082 / HC / NHLBI NIH HHS / United States
U01 HG004729 / HG / NHGRI NIH HHS / United States
1 R01 DK075787-01A1 / DK / NIDDK NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
HHSN268200782096C / HG / NHGRI NIH HHS / United States
HHSN268201100006C / HL / NHLBI NIH HHS / United States
/ / Intramural NIH HHS / United States
N01 HC-55222 / HC / NHLBI NIH HHS / United States
HHSN268201100008C / / PHS HHS / United States
U01 HG004422 / HG / NHGRI NIH HHS / United States
HHSN268201100012C / / PHS HHS / United States
U01HG04424 / HG / NHGRI NIH HHS / United States
M01RR00425 / RR / NCRR NIH HHS / United States
R01HL087641 / HL / NHLBI NIH HHS / United States
HHSN268201100005I / HL / NHLBI NIH HHS / United States
N01 AG062103 / AG / NIA NIH HHS / United States
N01-HC-85083 / HC / NHLBI NIH HHS / United States
U01DE018993 / DE / NIDCR NIH HHS / United States
N01-HC-75150 / HC / NHLBI NIH HHS / United States
U01HG004423 / HG / NHGRI NIH HHS / United States
N01-HC-85080 / HC / NHLBI NIH HHS / United States
U01 HL072515 / HL / NHLBI NIH HHS / United States
R01DK058845 / DK / NIDDK NIH HHS / United States
085475/B/08/Z / / Wellcome Trust / United Kingdom
M01 RR016500 / RR / NCRR NIH HHS / United States
HHSN268201100007C / / PHS HHS / United States
U01DE018903 / DE / NIDCR NIH HHS / United States
5R01HL08821502 / HL / NHLBI NIH HHS / United States
R01 CA047988 / CA / NCI NIH HHS / United States
U01HG004436 / HG / NHGRI NIH HHS / United States
M01 RR000425 / RR / NCRR NIH HHS / United States
U01HG004729 / HG / NHGRI NIH HHS / United States
U01 DE018903 / DE / NIDCR NIH HHS / United States
U01 HG004436 / HG / NHGRI NIH HHS / United States
N01HC75150 / HL / NHLBI NIH HHS / United States
U19 HL069757 / HL / NHLBI NIH HHS / United States
HHSN268201100009C / HL / NHLBI NIH HHS / United States
HHSN268201100011C / / PHS HHS / United States
5R01HL08770003 / HL / NHLBI NIH HHS / United States
HHSN268201100005C / HL / NHLBI NIH HHS / United States
U01 HG004735 / HG / NHGRI NIH HHS / United States
N01HC25195 / HL / NHLBI NIH HHS / United States
DK063491 / DK / NIDDK NIH HHS / United States
HHSN268201100007I / HL / NHLBI NIH HHS / United States
N01-HC-85079 / HC / NHLBI NIH HHS / United States
/ / Chief Scientist Office / United Kingdom
U01 HG004738 / HG / NHGRI NIH HHS / United States
HHSN268200782096C / / PHS HHS / United States
U01 HL072515-06 / HL / NHLBI NIH HHS / United States
U01 HG004423 / HG / NHGRI NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
HHSN268201100006C / / PHS HHS / United States
R01 HL087641 / HL / NHLBI NIH HHS / United States
R01 HL-87660 / HL / NHLBI NIH HHS / United States
N01 HC045133 / HC / NHLBI NIH HHS / United States
R01 DK066574 / DK / NIDDK NIH HHS / United States
U01 HL069757 / HL / NHLBI NIH HHS / United States
R01 AG018728 / AG / NIA NIH HHS / United States
U01 HG004399 / HG / NHGRI NIH HHS / United States
U01 GM074518 / GM / NIGMS NIH HHS / United States
N01 HC035129 / HC / NHLBI NIH HHS / United States
5R01DK07568102 / DK / NIDDK NIH HHS / United States
N01-HC-85084 / HC / NHLBI NIH HHS / United States
5R01DK06833603 / DK / NIDDK NIH HHS / United States
R01HL086694 / HL / NHLBI NIH HHS / United States
R01 HL088119 / HL / NHLBI NIH HHS / United States
U01 HG004726 / HG / NHGRI NIH HHS / United States

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