TY - JOUR
T1 - Genome-wide association and functional follow-up reveals new loci for kidney function
AU - Pattaro, Cristian
AU - Köttgen, Anna
AU - Teumer, Alexander
AU - Garnaas, Maija
AU - Böger, Carsten A
AU - Fuchsberger, Christian
AU - Olden, Matthias
AU - Chen, Ming-Huei
AU - Tin, Adrienne
AU - Taliun, Daniel
AU - Li, Man
AU - Gao, Xiaoyi
AU - Gorski, Mathias
AU - Yang, Qiong
AU - Hundertmark, Claudia
AU - Foster, Meredith C
AU - O'Seaghdha, Conall M
AU - Glazer, Nicole
AU - Isaacs, Aaron
AU - Liu, Ching-Ti
AU - Smith, Albert V
AU - O'Connell, Jeffrey R
AU - Struchalin, Maksim
AU - Tanaka, Toshiko
AU - Li, Guo
AU - Johnson, Andrew D
AU - Gierman, Hinco J
AU - Feitosa, Mary
AU - Hwang, Shih-Jen
AU - Atkinson, Elizabeth J
AU - Lohman, Kurt
AU - Cornelis, Marilyn C
AU - Johansson, Åsa
AU - Tönjes, Anke
AU - Dehghan, Abbas
AU - Chouraki, Vincent
AU - Holliday, Elizabeth G
AU - Sorice, Rossella
AU - Kutalik, Zoltan
AU - Lehtimäki, Terho
AU - Esko, Tõnu
AU - Deshmukh, Harshal
AU - Ulivi, Sheila
AU - Chu, Audrey Y
AU - Murgia, Federico
AU - Trompet, Stella
AU - Imboden, Medea
AU - Kollerits, Barbara
AU - Pistis, Giorgio
AU - Wang, Jie Jin
AU - CARDIoGRAM Consortium
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
KW - ATPases Associated with Diverse Cellular Activities
KW - African Americans/genetics
KW - Aged
KW - Animals
KW - Caspase 9/genetics
KW - Cyclin-Dependent Kinases/genetics
KW - DEAD-box RNA Helicases/genetics
KW - DNA Helicases/genetics
KW - DNA-Binding Proteins
KW - European Continental Ancestry Group/genetics
KW - Female
KW - Follow-Up Studies
KW - Gene Knockdown Techniques
KW - Genome-Wide Association Study
KW - Glomerular Filtration Rate/genetics
KW - Humans
KW - Kidney/physiopathology
KW - Kidney Failure, Chronic/genetics
KW - Male
KW - Middle Aged
KW - Phosphoric Diester Hydrolases/genetics
KW - Zebrafish/genetics
U2 - 10.1371/journal.pgen.1002584
DO - 10.1371/journal.pgen.1002584
M3 - Article
C2 - 22479191
SN - 1553-7390
VL - 8
SP - e1002584
JO - Plos Genetics
JF - Plos Genetics
IS - 3
ER -