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

AbstractHapMap imputed genome-wide association studies (GWAS) have revealed >50 loci at which common variants with minor allele frequency >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 < 5 × 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 < 0.05) genes and 127 significantly (FDR < 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 whole-genome sequencing becomes feasible in large samples.