Genome-Wide Association and Functional Follow-Up Reveals New Loci for Kidney Function | Zendy

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Genome-Wide Association and Functional Follow-Up Reveals New Loci for Kidney Function

Author(s) -

Cristian Pattaro,

Anna Köttgen,

Alexander Teumer,

Maija Garnaas,

Carsten A. Böger,

Christian Fuchsberger,

Matthias Olden,

MingHuei Chen,

Adrienne Tin,

Daniel Taliun,

Man Li,

Xiaoyi Gao,

Mathias Gorski,

Qiong Yang,

Claudia Hundertmark,

Meredith C. Foster,

Conall M. O’Seaghdha,

Nicole L. Glazer,

Aaron Isaacs,

Yongmei Liu,

Albert V. Smith,

Jeffrey R. O’Connell,

Maksim Struchalin,

Toshiko Tanaka,

Li Guo,

Andrew D. Johnson,

Hinco J. Gierman,

Mary F. Feitosa,

ShihJen Hwang,

Elizabeth J. Atkinson,

Kurt Lohman,

Marilyn C. Cornelis,

Åsa Johansson,

Anke Tönjes,

Abbas Dehghan,

Vincent Chouraki,

Elizabeth G. Holliday,

Rossella Sorice,

Zoltán Kutalik,

Terho Lehtimäki,

Tõnu Esko,

Harshal Deshmukh,

Sheila Ulivi,

Audrey Y. Chu,

Federico Murgia,

Stella Trompet,

Medea Imboden,

Barbara Kollerits,

Giorgio Pistis,

Tamara B. Harris,

Lenore J. Launer,

Thor Aspelund,

Guðný Eiríksdóttir,

Braxton D. Mitchell,

Eric Boerwinkle,

Helena Schmidt,

Margherita Cavalieri,

Madhumathi Rao,

Frank B. Hu,

Ayşe Demirkan,

Ben A. Oostra,

Mariza de Andrade,

Stephen T. Turner,

Jingzhong Ding,

Jeanette S. Andrews,

Barry I. Freedman,

Wolfgang Köenig,

Thomas Illig,

Angela Döring,

H.Erich Wichmann,

Ivana Kolčić,

Tatijana Zemunik,

Mladen Boban,

Cosetta Minelli,

Heather E. Wheeler,

Wilmar Igl,

Ghazal Zaboli,

Sarah H. Wild,

Alan F. Wright,

Harry Campbell,

David Ellinghaus,

Ute Nöthlings,

Gunnar Jacobs,

Reiner Biffar,

Karlhans Endlich,

Florian Ernst,

Georg Homuth,

Heyo K. Kroemer,

Matthias Nauck,

Sylvia Stracke,

Uwe Völker,

Henry Völzke,

Péter Kovács,

Michael Stümvoll,

Reedik Mägi,

Albert Hofman,

André G. Uitterlinden,

Fernando Rivadeneira,

Yurii S. Aulchenko,

Ozren Polašek,

Nick Hastie,

Véronique Vitart,

Catherine Helmer,

Jie Jin Wang,

Daniela Ruggiero,

Sven Bergmann,

Mika Kähönen,

Jorma Viikari,

Tiit Nikopensius,

Michael A. Province,

Shamika Ketkar,

Helen M. Colhoun,

Alex S. F. Doney,

Antonietta Robino,

Franco Giulianini,

Bernhard K. Krämer,

Laura Portas,

Ian Ford,

Brendan M. Buckley,

Martin Adam,

Gian Andri Thun,

Bernhard Paulweber,

Margot Haun,

Cinzia Sala,

Marie Metzger,

Paul Mitchell,

Marina Ciullo,

Stuart K. Kim,

Péter Vollenweider,

Olli T. Raitakari,

Andres Metspalu,

Nicholette D. Palmer,

Paolo Gasparini,

Mario Pirastu,

J. Wouter Jukema,

Nicole ProbstHensch,

Florian Kronenberg,

Daniela Toniolo,

Vilmundur Guðnason,

Alan R. Shuldiner,

Josef Coresh,

Reinhold Schmidt,

Luigi Ferrucci,

David S. Siscovick,

Cornelia M. van Duijn,

Ingrid B. Borecki,

Sharon L. R. Kardia,

Gary C. Curhan,

Igor Rudan,

Ulf Gyllensten,

James F. Wilson,

André Franke,

Peter P. Pramstaller,

Rainer Rettig,

Inga Prokopenko,

Jacqueline C.M. Witteman,

Caroline Hayward,

Paul M. Ridker,

Afshin Parsa,

Murielle Bochud,

Iris M. Heid,

Wolfram Goessling,

Daniel I. Chasman,

W.H. Linda Kao,

Caroline S. Fox

Publication year - 2012

Publication title -

plos genetics

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 3.587

H-Index - 233

eISSN - 1553-7404

pISSN - 1553-7390

DOI - 10.1371/journal.pgen.1002584

Subject(s) - biology , zebrafish , renal function , kidney disease , genome wide association study , genetic association , genetics , pathogenesis , gene , bioinformatics , single nucleotide polymorphism , endocrinology , genotype , immunology

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.

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