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Meta-Analysis of Genome-Wide Association Studies Identifies Six New Loci for Serum Calcium Concentrations
Calcium is vital to the normal functioning of multiple organ systems and its serum concentration is tightly regulated. Apart from CASR, the genes associated with serum calcium are largely unknown. We conducted a genome-wide association meta-analysis of 39,400 individuals from 17 population-based coh...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Public Library of Science
2013
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| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3778004/ https://www.ncbi.nlm.nih.gov/pubmed/24068962 http://dx.doi.org/10.1371/journal.pgen.1003796 |
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| author | O'Seaghdha, Conall M. Wu, Hongsheng Yang, Qiong Kapur, Karen Guessous, Idris Zuber, Annie Mercier Köttgen, Anna Stoudmann, Candice Teumer, Alexander Kutalik, Zoltán Mangino, Massimo Dehghan, Abbas Zhang, Weihua Eiriksdottir, Gudny Li, Guo Tanaka, Toshiko Portas, Laura Lopez, Lorna M. Hayward, Caroline Lohman, Kurt Matsuda, Koichi Padmanabhan, Sandosh Firsov, Dmitri Sorice, Rossella Ulivi, Sheila Brockhaus, A. Catharina Kleber, Marcus E. Mahajan, Anubha Ernst, Florian D. Gudnason, Vilmundur Launer, Lenore J. Mace, Aurelien Boerwinckle, Eric Arking, Dan E. Tanikawa, Chizu Nakamura, Yusuke Brown, Morris J. Gaspoz, Jean-Michel Theler, Jean-Marc Siscovick, David S. Psaty, Bruce M. Bergmann, Sven Vollenweider, Peter Vitart, Veronique Wright, Alan F. Zemunik, Tatijana Boban, Mladen Kolcic, Ivana Navarro, Pau Brown, Edward M. Estrada, Karol Ding, Jingzhong Harris, Tamara B. Bandinelli, Stefania Hernandez, Dena Singleton, Andrew B. Girotto, Giorgia Ruggiero, Daniela d'Adamo, Adamo Pio Robino, Antonietta Meitinger, Thomas Meisinger, Christa Davies, Gail Starr, John M. Chambers, John C. Boehm, Bernhard O. Winkelmann, Bernhard R. Huang, Jie Murgia, Federico Wild, Sarah H. Campbell, Harry Morris, Andrew P. Franco, Oscar H. Hofman, Albert Uitterlinden, Andre G. Rivadeneira, Fernando Völker, Uwe Hannemann, Anke Biffar, Reiner Hoffmann, Wolfgang Shin, So–Youn Lescuyer, Pierre Henry, Hughes Schurmann, Claudia Munroe, Patricia B. Gasparini, Paolo Pirastu, Nicola Ciullo, Marina Gieger, Christian März, Winfried Lind, Lars Spector, Tim D. Smith, Albert V. Rudan, Igor Wilson, James F. Polasek, Ozren Deary, Ian J. Pirastu, Mario Ferrucci, Luigi Liu, Yongmei Kestenbaum, Bryan Kooner, Jaspal S. Witteman, Jacqueline C. M. Nauck, Matthias Kao, W. H. Linda Wallaschofski, Henri Bonny, Olivier Fox, Caroline S. Bochud, Murielle |
| author_facet | O'Seaghdha, Conall M. Wu, Hongsheng Yang, Qiong Kapur, Karen Guessous, Idris Zuber, Annie Mercier Köttgen, Anna Stoudmann, Candice Teumer, Alexander Kutalik, Zoltán Mangino, Massimo Dehghan, Abbas Zhang, Weihua Eiriksdottir, Gudny Li, Guo Tanaka, Toshiko Portas, Laura Lopez, Lorna M. Hayward, Caroline Lohman, Kurt Matsuda, Koichi Padmanabhan, Sandosh Firsov, Dmitri Sorice, Rossella Ulivi, Sheila Brockhaus, A. Catharina Kleber, Marcus E. Mahajan, Anubha Ernst, Florian D. Gudnason, Vilmundur Launer, Lenore J. Mace, Aurelien Boerwinckle, Eric Arking, Dan E. Tanikawa, Chizu Nakamura, Yusuke Brown, Morris J. Gaspoz, Jean-Michel Theler, Jean-Marc Siscovick, David S. Psaty, Bruce M. Bergmann, Sven Vollenweider, Peter Vitart, Veronique Wright, Alan F. Zemunik, Tatijana Boban, Mladen Kolcic, Ivana Navarro, Pau Brown, Edward M. Estrada, Karol Ding, Jingzhong Harris, Tamara B. Bandinelli, Stefania Hernandez, Dena Singleton, Andrew B. Girotto, Giorgia Ruggiero, Daniela d'Adamo, Adamo Pio Robino, Antonietta Meitinger, Thomas Meisinger, Christa Davies, Gail Starr, John M. Chambers, John C. Boehm, Bernhard O. Winkelmann, Bernhard R. Huang, Jie Murgia, Federico Wild, Sarah H. Campbell, Harry Morris, Andrew P. Franco, Oscar H. Hofman, Albert Uitterlinden, Andre G. Rivadeneira, Fernando Völker, Uwe Hannemann, Anke Biffar, Reiner Hoffmann, Wolfgang Shin, So–Youn Lescuyer, Pierre Henry, Hughes Schurmann, Claudia Munroe, Patricia B. Gasparini, Paolo Pirastu, Nicola Ciullo, Marina Gieger, Christian März, Winfried Lind, Lars Spector, Tim D. Smith, Albert V. Rudan, Igor Wilson, James F. Polasek, Ozren Deary, Ian J. Pirastu, Mario Ferrucci, Luigi Liu, Yongmei Kestenbaum, Bryan Kooner, Jaspal S. Witteman, Jacqueline C. M. Nauck, Matthias Kao, W. H. Linda Wallaschofski, Henri Bonny, Olivier Fox, Caroline S. Bochud, Murielle |
| author_sort | O'Seaghdha, Conall M. |
| collection | PubMed |
| description | Calcium is vital to the normal functioning of multiple organ systems and its serum concentration is tightly regulated. Apart from CASR, the genes associated with serum calcium are largely unknown. We conducted a genome-wide association meta-analysis of 39,400 individuals from 17 population-based cohorts and investigated the 14 most strongly associated loci in ≤21,679 additional individuals. Seven loci (six new regions) in association with serum calcium were identified and replicated. Rs1570669 near CYP24A1 (P = 9.1E-12), rs10491003 upstream of GATA3 (P = 4.8E-09) and rs7481584 in CARS (P = 1.2E-10) implicate regions involved in Mendelian calcemic disorders: Rs1550532 in DGKD (P = 8.2E-11), also associated with bone density, and rs7336933 near DGKH/KIAA0564 (P = 9.1E-10) are near genes that encode distinct isoforms of diacylglycerol kinase. Rs780094 is in GCKR. We characterized the expression of these genes in gut, kidney, and bone, and demonstrate modulation of gene expression in bone in response to dietary calcium in mice. Our results shed new light on the genetics of calcium homeostasis. |
| format | Online Article Text |
| id | pubmed-3778004 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2013 |
| publisher | Public Library of Science |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-37780042013-09-25 Meta-Analysis of Genome-Wide Association Studies Identifies Six New Loci for Serum Calcium Concentrations O'Seaghdha, Conall M. Wu, Hongsheng Yang, Qiong Kapur, Karen Guessous, Idris Zuber, Annie Mercier Köttgen, Anna Stoudmann, Candice Teumer, Alexander Kutalik, Zoltán Mangino, Massimo Dehghan, Abbas Zhang, Weihua Eiriksdottir, Gudny Li, Guo Tanaka, Toshiko Portas, Laura Lopez, Lorna M. Hayward, Caroline Lohman, Kurt Matsuda, Koichi Padmanabhan, Sandosh Firsov, Dmitri Sorice, Rossella Ulivi, Sheila Brockhaus, A. Catharina Kleber, Marcus E. Mahajan, Anubha Ernst, Florian D. Gudnason, Vilmundur Launer, Lenore J. Mace, Aurelien Boerwinckle, Eric Arking, Dan E. Tanikawa, Chizu Nakamura, Yusuke Brown, Morris J. Gaspoz, Jean-Michel Theler, Jean-Marc Siscovick, David S. Psaty, Bruce M. Bergmann, Sven Vollenweider, Peter Vitart, Veronique Wright, Alan F. Zemunik, Tatijana Boban, Mladen Kolcic, Ivana Navarro, Pau Brown, Edward M. Estrada, Karol Ding, Jingzhong Harris, Tamara B. Bandinelli, Stefania Hernandez, Dena Singleton, Andrew B. Girotto, Giorgia Ruggiero, Daniela d'Adamo, Adamo Pio Robino, Antonietta Meitinger, Thomas Meisinger, Christa Davies, Gail Starr, John M. Chambers, John C. Boehm, Bernhard O. Winkelmann, Bernhard R. Huang, Jie Murgia, Federico Wild, Sarah H. Campbell, Harry Morris, Andrew P. Franco, Oscar H. Hofman, Albert Uitterlinden, Andre G. Rivadeneira, Fernando Völker, Uwe Hannemann, Anke Biffar, Reiner Hoffmann, Wolfgang Shin, So–Youn Lescuyer, Pierre Henry, Hughes Schurmann, Claudia Munroe, Patricia B. Gasparini, Paolo Pirastu, Nicola Ciullo, Marina Gieger, Christian März, Winfried Lind, Lars Spector, Tim D. Smith, Albert V. Rudan, Igor Wilson, James F. Polasek, Ozren Deary, Ian J. Pirastu, Mario Ferrucci, Luigi Liu, Yongmei Kestenbaum, Bryan Kooner, Jaspal S. Witteman, Jacqueline C. M. Nauck, Matthias Kao, W. H. Linda Wallaschofski, Henri Bonny, Olivier Fox, Caroline S. Bochud, Murielle PLoS Genet Research Article Calcium is vital to the normal functioning of multiple organ systems and its serum concentration is tightly regulated. Apart from CASR, the genes associated with serum calcium are largely unknown. We conducted a genome-wide association meta-analysis of 39,400 individuals from 17 population-based cohorts and investigated the 14 most strongly associated loci in ≤21,679 additional individuals. Seven loci (six new regions) in association with serum calcium were identified and replicated. Rs1570669 near CYP24A1 (P = 9.1E-12), rs10491003 upstream of GATA3 (P = 4.8E-09) and rs7481584 in CARS (P = 1.2E-10) implicate regions involved in Mendelian calcemic disorders: Rs1550532 in DGKD (P = 8.2E-11), also associated with bone density, and rs7336933 near DGKH/KIAA0564 (P = 9.1E-10) are near genes that encode distinct isoforms of diacylglycerol kinase. Rs780094 is in GCKR. We characterized the expression of these genes in gut, kidney, and bone, and demonstrate modulation of gene expression in bone in response to dietary calcium in mice. Our results shed new light on the genetics of calcium homeostasis. Public Library of Science 2013-09-19 /pmc/articles/PMC3778004/ /pubmed/24068962 http://dx.doi.org/10.1371/journal.pgen.1003796 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 O'Seaghdha, Conall M. Wu, Hongsheng Yang, Qiong Kapur, Karen Guessous, Idris Zuber, Annie Mercier Köttgen, Anna Stoudmann, Candice Teumer, Alexander Kutalik, Zoltán Mangino, Massimo Dehghan, Abbas Zhang, Weihua Eiriksdottir, Gudny Li, Guo Tanaka, Toshiko Portas, Laura Lopez, Lorna M. Hayward, Caroline Lohman, Kurt Matsuda, Koichi Padmanabhan, Sandosh Firsov, Dmitri Sorice, Rossella Ulivi, Sheila Brockhaus, A. Catharina Kleber, Marcus E. Mahajan, Anubha Ernst, Florian D. Gudnason, Vilmundur Launer, Lenore J. Mace, Aurelien Boerwinckle, Eric Arking, Dan E. Tanikawa, Chizu Nakamura, Yusuke Brown, Morris J. Gaspoz, Jean-Michel Theler, Jean-Marc Siscovick, David S. Psaty, Bruce M. Bergmann, Sven Vollenweider, Peter Vitart, Veronique Wright, Alan F. Zemunik, Tatijana Boban, Mladen Kolcic, Ivana Navarro, Pau Brown, Edward M. Estrada, Karol Ding, Jingzhong Harris, Tamara B. Bandinelli, Stefania Hernandez, Dena Singleton, Andrew B. Girotto, Giorgia Ruggiero, Daniela d'Adamo, Adamo Pio Robino, Antonietta Meitinger, Thomas Meisinger, Christa Davies, Gail Starr, John M. Chambers, John C. Boehm, Bernhard O. Winkelmann, Bernhard R. Huang, Jie Murgia, Federico Wild, Sarah H. Campbell, Harry Morris, Andrew P. Franco, Oscar H. Hofman, Albert Uitterlinden, Andre G. Rivadeneira, Fernando Völker, Uwe Hannemann, Anke Biffar, Reiner Hoffmann, Wolfgang Shin, So–Youn Lescuyer, Pierre Henry, Hughes Schurmann, Claudia Munroe, Patricia B. Gasparini, Paolo Pirastu, Nicola Ciullo, Marina Gieger, Christian März, Winfried Lind, Lars Spector, Tim D. Smith, Albert V. Rudan, Igor Wilson, James F. Polasek, Ozren Deary, Ian J. Pirastu, Mario Ferrucci, Luigi Liu, Yongmei Kestenbaum, Bryan Kooner, Jaspal S. Witteman, Jacqueline C. M. Nauck, Matthias Kao, W. H. Linda Wallaschofski, Henri Bonny, Olivier Fox, Caroline S. Bochud, Murielle Meta-Analysis of Genome-Wide Association Studies Identifies Six New Loci for Serum Calcium Concentrations |
| title | Meta-Analysis of Genome-Wide Association Studies Identifies Six New Loci for Serum Calcium Concentrations |
| title_full | Meta-Analysis of Genome-Wide Association Studies Identifies Six New Loci for Serum Calcium Concentrations |
| title_fullStr | Meta-Analysis of Genome-Wide Association Studies Identifies Six New Loci for Serum Calcium Concentrations |
| title_full_unstemmed | Meta-Analysis of Genome-Wide Association Studies Identifies Six New Loci for Serum Calcium Concentrations |
| title_short | Meta-Analysis of Genome-Wide Association Studies Identifies Six New Loci for Serum Calcium Concentrations |
| title_sort | meta-analysis of genome-wide association studies identifies six new loci for serum calcium concentrations |
| topic | Research Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3778004/ https://www.ncbi.nlm.nih.gov/pubmed/24068962 http://dx.doi.org/10.1371/journal.pgen.1003796 |
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