1000 Genomes-based meta-analysis identifies 10 novel loci for kidney function
Creators: name: Gorski, Mathias
name: van der Most, Peter J.
name: Teumer, Alexander
name: Chu, Audrey Y.
name: Li, Man
name: Mijatovic, Vladan
name: Nolte, Ilja M.
name: Cocca, Massimiliano
name: Taliun, Daniel
name: Gomez, Felicia
name: Li, Yong
name: Tayo, Bamidele
name: Tin, Adrienne
name: Feitosa, Mary F.
name: Aspelund, Thor
name: Attia, John
name: Biffar, Reiner
name: Bochud, Murielle
name: Boerwinkle, Eric
name: Borecki, Ingrid
name: Bottinger, Erwin P.
name: Chen, Ming-Huei
name: Chouraki, Vincent
name: Ciullo, Marina
name: Coresh, Josef
name: Cornelis, Marilyn C.
name: Curhan, Gary C.
name: d’Adamo, Adamo Pio
name: Dehghan, Abbas
name: Dengler, Laura
name: Ding, Jingzhong
name: Eiriksdottir, Gudny
name: Endlich, Karlhans
name: Enroth, Stefan
name: Esko, Tõnu
name: Franco, Oscar H.
name: Gasparini, Paolo
name: Gieger, Christian
name: Girotto, Giorgia
name: Gottesman, Omri
name: Gudnason, Vilmundur
name: Gyllensten, Ulf
name: Hancock, Stephen J.
name: Harris, Tamara B.
name: Helmer, Catherine
name: Höllerer, Simon
name: Hofer, Edith
name: Hofman, Albert
name: Holliday, Elizabeth G.
name: Homuth, Georg
name: Hu, Frank B.
name: Huth, Cornelia
name: Hutri-Kähönen, Nina
name: Hwang, Shih-Jen
name: Imboden, Medea
name: Johansson, Åsa
name: Kähönen, Mika
name: König, Wolfgang
name: Kramer, Holly
name: Krämer, Bernhard K.
name: Kumar, Ashish
name: Kutalik, Zoltan
name: Lambert, Jean-Charles
name: Launer, Lenore J.
name: Lehtimäki, Terho
name: de Borst, Martin
name: Navis, Gerjan
name: Swertz, Morris
name: Liu, Yongmei
name: Lohman, Kurt
name: Loos, Ruth J. F.
name: Lu, Yingchang
name: Lyytikäinen, Leo-Pekka
name: McEvoy, Mark A.
name: Meisinger, Christa
name: Meitinger, Thomas
name: Metspalu, Andres
name: Metzger, Marie
name: Mihailov, Evelin
name: Mitchell, Paul
name: Nauck, Matthias
name: Oldehinkel, Albertine J.
name: Olden, Matthias
name: Penninx, Brenda W. J. H.
name: Pistis, Giorgio
name: Pramstaller, Peter P.
name: Probst-Hensch, Nicole
name: Raitakari, Olli T.
name: Rettig, Rainer
name: Ridker, Paul M.
name: Rivadeneira, Fernando
name: Robino, Antonietta
name: Rosas, Sylvia E.
name: Ruderfer, Douglas
name: Ruggiero, Daniela
name: Saba, Yasaman
name: Sala, Cinzia
name: Schmidt, Helena
name: Schmidt, Reinhold
name: Scott, Rodney J.
name: Sedaghat, Sanaz
name: Smith, Albert V.
name: Sorice, Rossella
name: Stengel, Benedicte
name: Stracke, Sylvia
name: Strauch, Konstantin
name: Toniolo, Daniela
name: Uitterlinden, Andre G.
name: Ulivi, Sheila
name: Viikari, Jorma S.
name: Völker, Uwe
name: Vollenweider, Peter
name: Völzke, Henry
name: Vuckovic, Dragana
name: Waldenberger, Melanie
name: Jin Wang, Jie
name: Yang, Qiong
name: Chasman, Daniel I.
name: Tromp, Gerard
name: Snieder, Harold
name: Heid, Iris M.
name: Fox, Caroline S.
name: Köttgen, Anna
name: Pattaro, Cristian
name: Böger, Carsten A.
name: Fuchsberger, Christian
Publisher: name: Universität Regensburg
Year: 2017
Subjects: subject: GLOMERULAR-FILTRATION-RATE; COMMUNITY-BASED POPULATION; WIDE ASSOCIATION; SERUM CREATININE; GENOTYPE IMPUTATION; LINKAGE ANALYSIS; DISEASE; VARIANTS; INTEGRATION; HERITABILITY;
subject: 610 Medizin

description: HapMap imputed genome-wide association studies (GWAS) have revealed &gt; 50 loci at which common variants with minor allele frequency &gt; 5% are associated with kidney function. GWAS using more complete reference sets for imputation, such as those from The 1000 Genomes project, promise to identify novel loci that have been missed by previous efforts. To investigate the value of such a more complete variant catalog, we conducted a GWAS meta-analysis of kidney function based on the estimated glomerular filtration rate (eGFR) in 110,517 European ancestry participants using 1000 Genomes imputed data. We identified 10 novel loci with p-value &lt; 5 x 10(-8) previously missed by HapMap-based GWAS. Six of these loci (HOXD8, ARL15, PIK3R1, EYA4, ASTN2, and EPB41L3) are tagged by common SNPs unique to the 1000 Genomes reference panel. Using pathway analysis, we identified 39 significant (FDR &lt; 0.05) genes and 127 significantly (FDR &lt; 0.05) enriched gene sets, which were missed by our previous analyses. Among those, the 10 identified novel genes are part of pathways of kidney development, carbohydrate metabolism, cardiac septum development and glucose metabolism. These results highlight the utility of re-imputing from denser reference panels, until wholegenome sequencing becomes feasible in large samples.