¤ OpenAccess: Hybrid

This work has “Hybrid” OA status. This means it is free under an open license in a toll-access journal.

NFAT5 and SLC4A10 Loci Associate with Plasma Osmolality

Carsten A. Böger,Florian Kronenberg,Gearoid M. McMahon,Huichun Xu,Yen Chang,Peter J. van der Most,Gerjan Navis,Ilja M. Nolte,Martin H. de Borst,Weihua Zhang,Benjamin Lehne,Marie Loh,Sian Tsung Tan,Eric Boerwinkle,Morgan E. Grams,Peggy Sekula,Man Li,Beth Wilmot,James G. Moon,Paul Scheet,Francesco Cucca,Xiangjun Xiao,Leo Pekka Lyytikäinen,Graciela E. Delgado,Tanja B. Grammer,Marcus E. Kleber,Sanaz Sedaghat,Fernando Rivadeneira,Tanguy Corre,Zoltán Kutalik,Sven Bergmann,Carrie M. Nielson,Priya Srikanth,Alexander Teumer,Martina Müller‐Nurasyid,Anne Catharina Brockhaus,Arne Pfeufer,Wolfgang Rathmann,Annette Peters,Martha Matsumoto,Mariza de Andrade,Elizabeth J. Atkinson,Cassianne Robinson‐Cohen,Ian H. de Boer,Shih Jen Hwang,Iris M. Heid,Martin Gögele,Maria Pina Concas,Toshiko Tanaka,Stefania Bandinelli,Mike A. Nalls,Andrew Singleton,Salman M. Tajuddin,Adebowale Adeyemo,Jie Zhou,Ayo P. Doumatey,Shannon K. McWeeney,Joanne M. Murabito,Nora Franceschini,Michael F. Flessner,Michael G. Shlipak,James G. Wilson,Guanjie Chen,Charles N. Rotimi,Alan B. Zonderman,Michele K. Evans,Luigi Ferrucci,Olivier Devuyst,Mario Pirastu,Alan R. Shuldiner,Andrew A. Hicks,Peter P. Pramstaller,Bryan Kestenbaum,Sharon L. R. Kardia,Stephen T. Turner,Lifelines Cohort Study,Tamara Ellefson Briske,Christian Gieger,Konstantin Strauch,Christa Meisinger,Thomas Meitinger,Uwe Völker,Matthias Nauck,Henry Völzke,Péter Vollenweider,Murielle Bochud,Gérard Waeber,Mika Kähönen,Terho Lehtimäki,Winfried März,Abbas Dehghan,Oscar H. Franco,André G. Uitterlinden,Albert Hofman,Herman A. Taylor,John C. Chambers,Jaspal S. Kooner,Caroline S. Fox,Robert Hitzemann,Eric Orwoll,Cristian Pattaro,David Schlessinger,Anna Köttgen,Harold Snieder,Afshin Parsa,David Cohen

Genome-wide association study

Biology

Single-nucleotide polymorphism

2017

Disorders of water balance, an excess or deficit of total body water relative to body electrolyte content, are common and ascertained by plasma hypo- or hypernatremia, respectively. We performed a two-stage genome-wide association study meta-analysis on plasma sodium concentration in 45,889 individuals of European descent (stage 1 discovery) and 17,637 additional individuals of European descent (stage 2 replication), and a transethnic meta-analysis of replicated single-nucleotide polymorphisms in 79,506 individuals (63,526 individuals of European descent, 8765 individuals of Asian Indian descent, and 7215 individuals of African descent). In stage 1, we identified eight loci associated with plasma sodium concentration at P<5.0 × 10-6 Of these, rs9980 at NFAT5 replicated in stage 2 meta-analysis (P=3.1 × 10-5), with combined stages 1 and 2 genome-wide significance of P=5.6 × 10-10 Transethnic meta-analysis further supported the association at rs9980 (P=5.9 × 10-12). Additionally, rs16846053 at SLC4A10 showed nominally, but not genome-wide, significant association in combined stages 1 and 2 meta-analysis (P=6.7 × 10-8). NFAT5 encodes a ubiquitously expressed transcription factor that coordinates the intracellular response to hypertonic stress but was not previously implicated in the regulation of systemic water balance. SLC4A10 encodes a sodium bicarbonate transporter with a brain-restricted expression pattern, and variant rs16846053 affects a putative intronic NFAT5 DNA binding motif. The lead variants for NFAT5 and SLC4A10 are cis expression quantitative trait loci in tissues of the central nervous system and relevant to transcriptional regulation. Thus, genetic variation in NFAT5 and SLC4A10 expression and function in the central nervous system may affect the regulation of systemic water balance.

Cite this:

Generate Citation

“NFAT5 and SLC4A10 Loci Associate with Plasma Osmolality” is a paper by Carsten A. Böger Florian Kronenberg Gearoid M. McMahon Huichun Xu Yen Chang Peter J. van der Most Gerjan Navis Ilja M. Nolte Martin H. de Borst Weihua Zhang Benjamin Lehne Marie Loh Sian Tsung Tan Eric Boerwinkle Morgan E. Grams Peggy Sekula Man Li Beth Wilmot James G. Moon Paul Scheet Francesco Cucca Xiangjun Xiao Leo Pekka Lyytikäinen Graciela E. Delgado Tanja B. Grammer Marcus E. Kleber Sanaz Sedaghat Fernando Rivadeneira Tanguy Corre Zoltán Kutalik Sven Bergmann Carrie M. Nielson Priya Srikanth Alexander Teumer Martina Müller‐Nurasyid Anne Catharina Brockhaus Arne Pfeufer Wolfgang Rathmann Annette Peters Martha Matsumoto Mariza de Andrade Elizabeth J. Atkinson Cassianne Robinson‐Cohen Ian H. de Boer Shih Jen Hwang Iris M. Heid Martin Gögele Maria Pina Concas Toshiko Tanaka Stefania Bandinelli Mike A. Nalls Andrew Singleton Salman M. Tajuddin Adebowale Adeyemo Jie Zhou Ayo P. Doumatey Shannon K. McWeeney Joanne M. Murabito Nora Franceschini Michael F. Flessner Michael G. Shlipak James G. Wilson Guanjie Chen Charles N. Rotimi Alan B. Zonderman Michele K. Evans Luigi Ferrucci Olivier Devuyst Mario Pirastu Alan R. Shuldiner Andrew A. Hicks Peter P. Pramstaller Bryan Kestenbaum Sharon L. R. Kardia Stephen T. Turner Lifelines Cohort Study Tamara Ellefson Briske Christian Gieger Konstantin Strauch Christa Meisinger Thomas Meitinger Uwe Völker Matthias Nauck Henry Völzke Péter Vollenweider Murielle Bochud Gérard Waeber Mika Kähönen Terho Lehtimäki Winfried März Abbas Dehghan Oscar H. Franco André G. Uitterlinden Albert Hofman Herman A. Taylor John C. Chambers Jaspal S. Kooner Caroline S. Fox Robert Hitzemann Eric Orwoll Cristian Pattaro David Schlessinger Anna Köttgen Harold Snieder Afshin Parsa David Cohen published in 2017. It has an Open Access status of “hybrid”. You can read and download a PDF Full Text of this paper here.