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Modulation of Genetic Associations with Serum Urate Levels by Body-Mass-Index in Humans

We tested for interactions between body mass index (BMI) and common genetic variants affecting serum urate levels, genome-wide, in up to 42569 participants. Both stratified genome-wide association (GWAS) analyses, in lean, overweight and obese individuals, and regression-type analyses in a non BMI-s...

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Autores principales: Huffman, Jennifer E., Albrecht, Eva, Teumer, Alexander, Mangino, Massimo, Kapur, Karen, Johnson, Toby, Kutalik, Zoltán, Pirastu, Nicola, Pistis, Giorgio, Lopez, Lorna M., Haller, Toomas, Salo, Perttu, Goel, Anuj, Li, Man, Tanaka, Toshiko, Dehghan, Abbas, Ruggiero, Daniela, Malerba, Giovanni, Smith, Albert V., Nolte, Ilja M., Portas, Laura, Phipps-Green, Amanda, Boteva, Lora, Navarro, Pau, Johansson, Asa, Hicks, Andrew A., Polasek, Ozren, Esko, Tõnu, Peden, John F., Harris, Sarah E., Murgia, Federico, Wild, Sarah H., Tenesa, Albert, Tin, Adrienne, Mihailov, Evelin, Grotevendt, Anne, Gislason, Gauti K., Coresh, Josef, D'Adamo, Pio, Ulivi, Sheila, Vollenweider, Peter, Waeber, Gerard, Campbell, Susan, Kolcic, Ivana, Fisher, Krista, Viigimaa, Margus, Metter, Jeffrey E., Masciullo, Corrado, Trabetti, Elisabetta, Bombieri, Cristina, Sorice, Rossella, Döring, Angela, Reischl, Eva, Strauch, Konstantin, Hofman, Albert, Uitterlinden, Andre G., Waldenberger, Melanie, Wichmann, H-Erich, Davies, Gail, Gow, Alan J., Dalbeth, Nicola, Stamp, Lisa, Smit, Johannes H., Kirin, Mirna, Nagaraja, Ramaiah, Nauck, Matthias, Schurmann, Claudia, Budde, Kathrin, Farrington, Susan M., Theodoratou, Evropi, Jula, Antti, Salomaa, Veikko, Sala, Cinzia, Hengstenberg, Christian, Burnier, Michel, Mägi, Reedik, Klopp, Norman, Kloiber, Stefan, Schipf, Sabine, Ripatti, Samuli, Cabras, Stefano, Soranzo, Nicole, Homuth, Georg, Nutile, Teresa, Munroe, Patricia B., Hastie, Nicholas, Campbell, Harry, Rudan, Igor, Cabrera, Claudia, Haley, Chris, Franco, Oscar H., Merriman, Tony R., Gudnason, Vilmundur, Pirastu, Mario, Penninx, Brenda W., Snieder, Harold, Metspalu, Andres, Ciullo, Marina, Pramstaller, Peter P., van Duijn, Cornelia M., Ferrucci, Luigi, Gambaro, Giovanni, Deary, Ian J., Dunlop, Malcolm G., Wilson, James F., Gasparini, Paolo, Gyllensten, Ulf, Spector, Tim D., Wright, Alan F., Hayward, Caroline, Watkins, Hugh, Perola, Markus, Bochud, Murielle, Kao, W. H. Linda, Caulfield, Mark, Toniolo, Daniela, Völzke, Henry, Gieger, Christian, Köttgen, Anna, Vitart, Veronique
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4374966/
https://www.ncbi.nlm.nih.gov/pubmed/25811787
http://dx.doi.org/10.1371/journal.pone.0119752
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author Huffman, Jennifer E.
Albrecht, Eva
Teumer, Alexander
Mangino, Massimo
Kapur, Karen
Johnson, Toby
Kutalik, Zoltán
Pirastu, Nicola
Pistis, Giorgio
Lopez, Lorna M.
Haller, Toomas
Salo, Perttu
Goel, Anuj
Li, Man
Tanaka, Toshiko
Dehghan, Abbas
Ruggiero, Daniela
Malerba, Giovanni
Smith, Albert V.
Nolte, Ilja M.
Portas, Laura
Phipps-Green, Amanda
Boteva, Lora
Navarro, Pau
Johansson, Asa
Hicks, Andrew A.
Polasek, Ozren
Esko, Tõnu
Peden, John F.
Harris, Sarah E.
Murgia, Federico
Wild, Sarah H.
Tenesa, Albert
Tin, Adrienne
Mihailov, Evelin
Grotevendt, Anne
Gislason, Gauti K.
Coresh, Josef
D'Adamo, Pio
Ulivi, Sheila
Vollenweider, Peter
Waeber, Gerard
Campbell, Susan
Kolcic, Ivana
Fisher, Krista
Viigimaa, Margus
Metter, Jeffrey E.
Masciullo, Corrado
Trabetti, Elisabetta
Bombieri, Cristina
Sorice, Rossella
Döring, Angela
Reischl, Eva
Strauch, Konstantin
Hofman, Albert
Uitterlinden, Andre G.
Waldenberger, Melanie
Wichmann, H-Erich
Davies, Gail
Gow, Alan J.
Dalbeth, Nicola
Stamp, Lisa
Smit, Johannes H.
Kirin, Mirna
Nagaraja, Ramaiah
Nauck, Matthias
Schurmann, Claudia
Budde, Kathrin
Farrington, Susan M.
Theodoratou, Evropi
Jula, Antti
Salomaa, Veikko
Sala, Cinzia
Hengstenberg, Christian
Burnier, Michel
Mägi, Reedik
Klopp, Norman
Kloiber, Stefan
Schipf, Sabine
Ripatti, Samuli
Cabras, Stefano
Soranzo, Nicole
Homuth, Georg
Nutile, Teresa
Munroe, Patricia B.
Hastie, Nicholas
Campbell, Harry
Rudan, Igor
Cabrera, Claudia
Haley, Chris
Franco, Oscar H.
Merriman, Tony R.
Gudnason, Vilmundur
Pirastu, Mario
Penninx, Brenda W.
Snieder, Harold
Metspalu, Andres
Ciullo, Marina
Pramstaller, Peter P.
van Duijn, Cornelia M.
Ferrucci, Luigi
Gambaro, Giovanni
Deary, Ian J.
Dunlop, Malcolm G.
Wilson, James F.
Gasparini, Paolo
Gyllensten, Ulf
Spector, Tim D.
Wright, Alan F.
Hayward, Caroline
Watkins, Hugh
Perola, Markus
Bochud, Murielle
Kao, W. H. Linda
Caulfield, Mark
Toniolo, Daniela
Völzke, Henry
Gieger, Christian
Köttgen, Anna
Vitart, Veronique
author_facet Huffman, Jennifer E.
Albrecht, Eva
Teumer, Alexander
Mangino, Massimo
Kapur, Karen
Johnson, Toby
Kutalik, Zoltán
Pirastu, Nicola
Pistis, Giorgio
Lopez, Lorna M.
Haller, Toomas
Salo, Perttu
Goel, Anuj
Li, Man
Tanaka, Toshiko
Dehghan, Abbas
Ruggiero, Daniela
Malerba, Giovanni
Smith, Albert V.
Nolte, Ilja M.
Portas, Laura
Phipps-Green, Amanda
Boteva, Lora
Navarro, Pau
Johansson, Asa
Hicks, Andrew A.
Polasek, Ozren
Esko, Tõnu
Peden, John F.
Harris, Sarah E.
Murgia, Federico
Wild, Sarah H.
Tenesa, Albert
Tin, Adrienne
Mihailov, Evelin
Grotevendt, Anne
Gislason, Gauti K.
Coresh, Josef
D'Adamo, Pio
Ulivi, Sheila
Vollenweider, Peter
Waeber, Gerard
Campbell, Susan
Kolcic, Ivana
Fisher, Krista
Viigimaa, Margus
Metter, Jeffrey E.
Masciullo, Corrado
Trabetti, Elisabetta
Bombieri, Cristina
Sorice, Rossella
Döring, Angela
Reischl, Eva
Strauch, Konstantin
Hofman, Albert
Uitterlinden, Andre G.
Waldenberger, Melanie
Wichmann, H-Erich
Davies, Gail
Gow, Alan J.
Dalbeth, Nicola
Stamp, Lisa
Smit, Johannes H.
Kirin, Mirna
Nagaraja, Ramaiah
Nauck, Matthias
Schurmann, Claudia
Budde, Kathrin
Farrington, Susan M.
Theodoratou, Evropi
Jula, Antti
Salomaa, Veikko
Sala, Cinzia
Hengstenberg, Christian
Burnier, Michel
Mägi, Reedik
Klopp, Norman
Kloiber, Stefan
Schipf, Sabine
Ripatti, Samuli
Cabras, Stefano
Soranzo, Nicole
Homuth, Georg
Nutile, Teresa
Munroe, Patricia B.
Hastie, Nicholas
Campbell, Harry
Rudan, Igor
Cabrera, Claudia
Haley, Chris
Franco, Oscar H.
Merriman, Tony R.
Gudnason, Vilmundur
Pirastu, Mario
Penninx, Brenda W.
Snieder, Harold
Metspalu, Andres
Ciullo, Marina
Pramstaller, Peter P.
van Duijn, Cornelia M.
Ferrucci, Luigi
Gambaro, Giovanni
Deary, Ian J.
Dunlop, Malcolm G.
Wilson, James F.
Gasparini, Paolo
Gyllensten, Ulf
Spector, Tim D.
Wright, Alan F.
Hayward, Caroline
Watkins, Hugh
Perola, Markus
Bochud, Murielle
Kao, W. H. Linda
Caulfield, Mark
Toniolo, Daniela
Völzke, Henry
Gieger, Christian
Köttgen, Anna
Vitart, Veronique
author_sort Huffman, Jennifer E.
collection PubMed
description We tested for interactions between body mass index (BMI) and common genetic variants affecting serum urate levels, genome-wide, in up to 42569 participants. Both stratified genome-wide association (GWAS) analyses, in lean, overweight and obese individuals, and regression-type analyses in a non BMI-stratified overall sample were performed. The former did not uncover any novel locus with a major main effect, but supported modulation of effects for some known and potentially new urate loci. The latter highlighted a SNP at RBFOX3 reaching genome-wide significant level (effect size 0.014, 95% CI 0.008-0.02, P(inter)= 2.6 x 10(-8)). Two top loci in interaction term analyses, RBFOX3 and ERO1LB-EDARADD, also displayed suggestive differences in main effect size between the lean and obese strata. All top ranking loci for urate effect differences between BMI categories were novel and most had small magnitude but opposite direction effects between strata. They include the locus RBMS1-TANK (men, P(difflean-overweight)= 4.7 x 10(-8)), a region that has been associated with several obesity related traits, and TSPYL5 (men, P(difflean-overweight)= 9.1 x 10(-8)), regulating adipocytes-produced estradiol. The top-ranking known urate loci was ABCG2, the strongest known gout risk locus, with an effect halved in obese compared to lean men (P(difflean-obese)= 2 x 10(-4)). Finally, pathway analysis suggested a role for N-glycan biosynthesis as a prominent urate-associated pathway in the lean stratum. These results illustrate a potentially powerful way to monitor changes occurring in obesogenic environment.
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spelling pubmed-43749662015-04-04 Modulation of Genetic Associations with Serum Urate Levels by Body-Mass-Index in Humans Huffman, Jennifer E. Albrecht, Eva Teumer, Alexander Mangino, Massimo Kapur, Karen Johnson, Toby Kutalik, Zoltán Pirastu, Nicola Pistis, Giorgio Lopez, Lorna M. Haller, Toomas Salo, Perttu Goel, Anuj Li, Man Tanaka, Toshiko Dehghan, Abbas Ruggiero, Daniela Malerba, Giovanni Smith, Albert V. Nolte, Ilja M. Portas, Laura Phipps-Green, Amanda Boteva, Lora Navarro, Pau Johansson, Asa Hicks, Andrew A. Polasek, Ozren Esko, Tõnu Peden, John F. Harris, Sarah E. Murgia, Federico Wild, Sarah H. Tenesa, Albert Tin, Adrienne Mihailov, Evelin Grotevendt, Anne Gislason, Gauti K. Coresh, Josef D'Adamo, Pio Ulivi, Sheila Vollenweider, Peter Waeber, Gerard Campbell, Susan Kolcic, Ivana Fisher, Krista Viigimaa, Margus Metter, Jeffrey E. Masciullo, Corrado Trabetti, Elisabetta Bombieri, Cristina Sorice, Rossella Döring, Angela Reischl, Eva Strauch, Konstantin Hofman, Albert Uitterlinden, Andre G. Waldenberger, Melanie Wichmann, H-Erich Davies, Gail Gow, Alan J. Dalbeth, Nicola Stamp, Lisa Smit, Johannes H. Kirin, Mirna Nagaraja, Ramaiah Nauck, Matthias Schurmann, Claudia Budde, Kathrin Farrington, Susan M. Theodoratou, Evropi Jula, Antti Salomaa, Veikko Sala, Cinzia Hengstenberg, Christian Burnier, Michel Mägi, Reedik Klopp, Norman Kloiber, Stefan Schipf, Sabine Ripatti, Samuli Cabras, Stefano Soranzo, Nicole Homuth, Georg Nutile, Teresa Munroe, Patricia B. Hastie, Nicholas Campbell, Harry Rudan, Igor Cabrera, Claudia Haley, Chris Franco, Oscar H. Merriman, Tony R. Gudnason, Vilmundur Pirastu, Mario Penninx, Brenda W. Snieder, Harold Metspalu, Andres Ciullo, Marina Pramstaller, Peter P. van Duijn, Cornelia M. Ferrucci, Luigi Gambaro, Giovanni Deary, Ian J. Dunlop, Malcolm G. Wilson, James F. Gasparini, Paolo Gyllensten, Ulf Spector, Tim D. Wright, Alan F. Hayward, Caroline Watkins, Hugh Perola, Markus Bochud, Murielle Kao, W. H. Linda Caulfield, Mark Toniolo, Daniela Völzke, Henry Gieger, Christian Köttgen, Anna Vitart, Veronique PLoS One Research Article We tested for interactions between body mass index (BMI) and common genetic variants affecting serum urate levels, genome-wide, in up to 42569 participants. Both stratified genome-wide association (GWAS) analyses, in lean, overweight and obese individuals, and regression-type analyses in a non BMI-stratified overall sample were performed. The former did not uncover any novel locus with a major main effect, but supported modulation of effects for some known and potentially new urate loci. The latter highlighted a SNP at RBFOX3 reaching genome-wide significant level (effect size 0.014, 95% CI 0.008-0.02, P(inter)= 2.6 x 10(-8)). Two top loci in interaction term analyses, RBFOX3 and ERO1LB-EDARADD, also displayed suggestive differences in main effect size between the lean and obese strata. All top ranking loci for urate effect differences between BMI categories were novel and most had small magnitude but opposite direction effects between strata. They include the locus RBMS1-TANK (men, P(difflean-overweight)= 4.7 x 10(-8)), a region that has been associated with several obesity related traits, and TSPYL5 (men, P(difflean-overweight)= 9.1 x 10(-8)), regulating adipocytes-produced estradiol. The top-ranking known urate loci was ABCG2, the strongest known gout risk locus, with an effect halved in obese compared to lean men (P(difflean-obese)= 2 x 10(-4)). Finally, pathway analysis suggested a role for N-glycan biosynthesis as a prominent urate-associated pathway in the lean stratum. These results illustrate a potentially powerful way to monitor changes occurring in obesogenic environment. Public Library of Science 2015-03-26 /pmc/articles/PMC4374966/ /pubmed/25811787 http://dx.doi.org/10.1371/journal.pone.0119752 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
spellingShingle Research Article
Huffman, Jennifer E.
Albrecht, Eva
Teumer, Alexander
Mangino, Massimo
Kapur, Karen
Johnson, Toby
Kutalik, Zoltán
Pirastu, Nicola
Pistis, Giorgio
Lopez, Lorna M.
Haller, Toomas
Salo, Perttu
Goel, Anuj
Li, Man
Tanaka, Toshiko
Dehghan, Abbas
Ruggiero, Daniela
Malerba, Giovanni
Smith, Albert V.
Nolte, Ilja M.
Portas, Laura
Phipps-Green, Amanda
Boteva, Lora
Navarro, Pau
Johansson, Asa
Hicks, Andrew A.
Polasek, Ozren
Esko, Tõnu
Peden, John F.
Harris, Sarah E.
Murgia, Federico
Wild, Sarah H.
Tenesa, Albert
Tin, Adrienne
Mihailov, Evelin
Grotevendt, Anne
Gislason, Gauti K.
Coresh, Josef
D'Adamo, Pio
Ulivi, Sheila
Vollenweider, Peter
Waeber, Gerard
Campbell, Susan
Kolcic, Ivana
Fisher, Krista
Viigimaa, Margus
Metter, Jeffrey E.
Masciullo, Corrado
Trabetti, Elisabetta
Bombieri, Cristina
Sorice, Rossella
Döring, Angela
Reischl, Eva
Strauch, Konstantin
Hofman, Albert
Uitterlinden, Andre G.
Waldenberger, Melanie
Wichmann, H-Erich
Davies, Gail
Gow, Alan J.
Dalbeth, Nicola
Stamp, Lisa
Smit, Johannes H.
Kirin, Mirna
Nagaraja, Ramaiah
Nauck, Matthias
Schurmann, Claudia
Budde, Kathrin
Farrington, Susan M.
Theodoratou, Evropi
Jula, Antti
Salomaa, Veikko
Sala, Cinzia
Hengstenberg, Christian
Burnier, Michel
Mägi, Reedik
Klopp, Norman
Kloiber, Stefan
Schipf, Sabine
Ripatti, Samuli
Cabras, Stefano
Soranzo, Nicole
Homuth, Georg
Nutile, Teresa
Munroe, Patricia B.
Hastie, Nicholas
Campbell, Harry
Rudan, Igor
Cabrera, Claudia
Haley, Chris
Franco, Oscar H.
Merriman, Tony R.
Gudnason, Vilmundur
Pirastu, Mario
Penninx, Brenda W.
Snieder, Harold
Metspalu, Andres
Ciullo, Marina
Pramstaller, Peter P.
van Duijn, Cornelia M.
Ferrucci, Luigi
Gambaro, Giovanni
Deary, Ian J.
Dunlop, Malcolm G.
Wilson, James F.
Gasparini, Paolo
Gyllensten, Ulf
Spector, Tim D.
Wright, Alan F.
Hayward, Caroline
Watkins, Hugh
Perola, Markus
Bochud, Murielle
Kao, W. H. Linda
Caulfield, Mark
Toniolo, Daniela
Völzke, Henry
Gieger, Christian
Köttgen, Anna
Vitart, Veronique
Modulation of Genetic Associations with Serum Urate Levels by Body-Mass-Index in Humans
title Modulation of Genetic Associations with Serum Urate Levels by Body-Mass-Index in Humans
title_full Modulation of Genetic Associations with Serum Urate Levels by Body-Mass-Index in Humans
title_fullStr Modulation of Genetic Associations with Serum Urate Levels by Body-Mass-Index in Humans
title_full_unstemmed Modulation of Genetic Associations with Serum Urate Levels by Body-Mass-Index in Humans
title_short Modulation of Genetic Associations with Serum Urate Levels by Body-Mass-Index in Humans
title_sort modulation of genetic associations with serum urate levels by body-mass-index in humans
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4374966/
https://www.ncbi.nlm.nih.gov/pubmed/25811787
http://dx.doi.org/10.1371/journal.pone.0119752
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AT haleychris modulationofgeneticassociationswithserumuratelevelsbybodymassindexinhumans
AT francooscarh modulationofgeneticassociationswithserumuratelevelsbybodymassindexinhumans
AT merrimantonyr modulationofgeneticassociationswithserumuratelevelsbybodymassindexinhumans
AT gudnasonvilmundur modulationofgeneticassociationswithserumuratelevelsbybodymassindexinhumans
AT pirastumario modulationofgeneticassociationswithserumuratelevelsbybodymassindexinhumans
AT penninxbrendaw modulationofgeneticassociationswithserumuratelevelsbybodymassindexinhumans
AT sniederharold modulationofgeneticassociationswithserumuratelevelsbybodymassindexinhumans
AT metspaluandres modulationofgeneticassociationswithserumuratelevelsbybodymassindexinhumans
AT ciullomarina modulationofgeneticassociationswithserumuratelevelsbybodymassindexinhumans
AT pramstallerpeterp modulationofgeneticassociationswithserumuratelevelsbybodymassindexinhumans
AT vanduijncorneliam modulationofgeneticassociationswithserumuratelevelsbybodymassindexinhumans
AT ferrucciluigi modulationofgeneticassociationswithserumuratelevelsbybodymassindexinhumans
AT gambarogiovanni modulationofgeneticassociationswithserumuratelevelsbybodymassindexinhumans
AT dearyianj modulationofgeneticassociationswithserumuratelevelsbybodymassindexinhumans
AT dunlopmalcolmg modulationofgeneticassociationswithserumuratelevelsbybodymassindexinhumans
AT wilsonjamesf modulationofgeneticassociationswithserumuratelevelsbybodymassindexinhumans
AT gasparinipaolo modulationofgeneticassociationswithserumuratelevelsbybodymassindexinhumans
AT gyllenstenulf modulationofgeneticassociationswithserumuratelevelsbybodymassindexinhumans
AT spectortimd modulationofgeneticassociationswithserumuratelevelsbybodymassindexinhumans
AT wrightalanf modulationofgeneticassociationswithserumuratelevelsbybodymassindexinhumans
AT haywardcaroline modulationofgeneticassociationswithserumuratelevelsbybodymassindexinhumans
AT watkinshugh modulationofgeneticassociationswithserumuratelevelsbybodymassindexinhumans
AT perolamarkus modulationofgeneticassociationswithserumuratelevelsbybodymassindexinhumans
AT bochudmurielle modulationofgeneticassociationswithserumuratelevelsbybodymassindexinhumans
AT kaowhlinda modulationofgeneticassociationswithserumuratelevelsbybodymassindexinhumans
AT caulfieldmark modulationofgeneticassociationswithserumuratelevelsbybodymassindexinhumans
AT toniolodaniela modulationofgeneticassociationswithserumuratelevelsbybodymassindexinhumans
AT volzkehenry modulationofgeneticassociationswithserumuratelevelsbybodymassindexinhumans
AT giegerchristian modulationofgeneticassociationswithserumuratelevelsbybodymassindexinhumans
AT kottgenanna modulationofgeneticassociationswithserumuratelevelsbybodymassindexinhumans
AT vitartveronique modulationofgeneticassociationswithserumuratelevelsbybodymassindexinhumans