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Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

ABSTRACT: Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.

SUBMITTER: Pattaro C

PROVIDER: S-EPMC4735748 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

Pattaro Cristian C Teumer Alexander A Gorski Mathias M Chu Audrey Y AY Li Man M Mijatovic Vladan V Garnaas Maija M Tin Adrienne A Sorice Rossella R Li Yong Y Taliun Daniel D Olden Matthias M Foster Meredith M Yang Qiong Q Chen Ming-Huei MH Pers Tune H TH Johnson Andrew D AD Ko Yi-An YA Fuchsberger Christian C Tayo Bamidele B Nalls Michael M Feitosa Mary F MF Isaacs Aaron A Dehghan Abbas A d'Adamo Pio P Adeyemo Adebowale A Dieffenbach Aida Karina AK Zonderman Alan B AB Nolte Ilja M IM van der Most Peter J PJ Wright Alan F AF Shuldiner Alan R AR Morrison Alanna C AC Hofman Albert A Smith Albert V AV Dreisbach Albert W AW Franke Andre A Uitterlinden Andre G AG Metspalu Andres A Tonjes Anke A Lupo Antonio A Robino Antonietta A Johansson Åsa Å Demirkan Ayse A Kollerits Barbara B Freedman Barry I BI Ponte Belen B Oostra Ben A BA Paulweber Bernhard B Krämer Bernhard K BK Mitchell Braxton D BD Buckley Brendan M BM Peralta Carmen A CA Hayward Caroline C Helmer Catherine C Rotimi Charles N CN Shaffer Christian M CM Müller Christian C Sala Cinzia C van Duijn Cornelia M CM Saint-Pierre Aude A Ackermann Daniel D Shriner Daniel D Ruggiero Daniela D Toniolo Daniela D Lu Yingchang Y Cusi Daniele D Czamara Darina D Ellinghaus David D Siscovick David S DS Ruderfer Douglas D Gieger Christian C Grallert Harald H Rochtchina Elena E Atkinson Elizabeth J EJ Holliday Elizabeth G EG Boerwinkle Eric E Salvi Erika E Bottinger Erwin P EP Murgia Federico F Rivadeneira Fernando F Ernst Florian F Kronenberg Florian F Hu Frank B FB Navis Gerjan J GJ Curhan Gary C GC Ehret George B GB Homuth Georg G Coassin Stefan S Thun Gian-Andri GA Pistis Giorgio G Gambaro Giovanni G Malerba Giovanni G Montgomery Grant W GW Eiriksdottir Gudny G Jacobs Gunnar G Li Guo G Wichmann H-Erich HE Campbell Harry H Schmidt Helena H Wallaschofski Henri H Völzke Henry H Brenner Hermann H Kroemer Heyo K HK Kramer Holly H Lin Honghuang H Leach I Mateo IM Ford Ian I Guessous Idris I Rudan Igor I Prokopenko Inga I Borecki Ingrid I Heid Iris M IM Kolcic Ivana I Persico Ivana I Jukema J Wouter JW Wilson James F JF Felix Janine F JF Divers Jasmin J Lambert Jean-Charles JC Stafford Jeanette M JM Gaspoz Jean-Michel JM Smith Jennifer A JA Faul Jessica D JD Wang Jie Jin JJ Ding Jingzhong J Hirschhorn Joel N JN Attia John J Whitfield John B JB Chalmers John J Viikari Jorma J Coresh Josef J Denny Joshua C JC Karjalainen Juha J Fernandes Jyotika K JK Endlich Karlhans K Butterbach Katja K Keene Keith L KL Lohman Kurt K Portas Laura L Launer Lenore J LJ Lyytikäinen Leo-Pekka LP Yengo Loic L Franke Lude L Ferrucci Luigi L Rose Lynda M LM Kedenko Lyudmyla L Rao Madhumathi M Struchalin Maksim M Kleber Marcus E ME Cavalieri Margherita M Haun Margot M Cornelis Marilyn C MC Ciullo Marina M Pirastu Mario M de Andrade Mariza M McEvoy Mark A MA Woodward Mark M Adam Martin M Cocca Massimiliano M Nauck Matthias M Imboden Medea M Waldenberger Melanie M Pruijm Menno M Metzger Marie M Stumvoll Michael M Evans Michele K MK Sale Michele M MM Kähönen Mika M Boban Mladen M Bochud Murielle M Rheinberger Myriam M Verweij Niek N Bouatia-Naji Nabila N Martin Nicholas G NG Hastie Nick N Probst-Hensch Nicole N Soranzo Nicole N Devuyst Olivier O Raitakari Olli O Gottesman Omri O Franco Oscar H OH Polasek Ozren O Gasparini Paolo P Munroe Patricia B PB Ridker Paul M PM Mitchell Paul P Muntner Paul P Meisinger Christa C Smit Johannes H JH Kovacs Peter P Wild Philipp S PS Froguel Philippe P Rettig Rainer R Mägi Reedik R Biffar Reiner R Schmidt Reinhold R Middelberg Rita P S RP Carroll Robert J RJ Penninx Brenda W BW Scott Rodney J RJ Katz Ronit R Sedaghat Sanaz S Wild Sarah H SH Kardia Sharon L R SL Ulivi Sheila S Hwang Shih-Jen SJ Enroth Stefan S Kloiber Stefan S Trompet Stella S Stengel Benedicte B Hancock Stephen J SJ Turner Stephen T ST Rosas Sylvia E SE Stracke Sylvia S Harris Tamara B TB Zeller Tanja T Zemunik Tatijana T Lehtimäki Terho T Illig Thomas T Aspelund Thor T Nikopensius Tiit T Esko Tonu T Tanaka Toshiko T Gyllensten Ulf U Völker Uwe U Emilsson Valur V Vitart Veronique V Aalto Ville V Gudnason Vilmundur V Chouraki Vincent V Chen Wei-Min WM Igl Wilmar W März Winfried W Koenig Wolfgang W Lieb Wolfgang W Loos Ruth J F RJ Liu Yongmei Y Snieder Harold H Pramstaller Peter P PP Parsa Afshin A O'Connell Jeffrey R JR Susztak Katalin K Hamet Pavel P Tremblay Johanne J de Boer Ian H IH Böger Carsten A CA Goessling Wolfram W Chasman Daniel I DI Köttgen Anna A Kao W H Linda WH Fox Caroline S CS

Nature communications 20160121

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that ...[more]

PMID: 26831199

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Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

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Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

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