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    Meta-Analysis of Genome-Wide Association Studies Identifies Six New Loci for Serum Calcium Concentrations


    Abecasis, Gonçalo, 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. and Bochud, Murielle (2013) Meta-Analysis of Genome-Wide Association Studies Identifies Six New Loci for Serum Calcium Concentrations. PLoS Genetics, 9 (9). e1003796. ISSN 1553-7404

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    Abstract

    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.
    Item Type: Article
    Keywords: Meta-Analysis; Genome-Wide; Association Studies; Identifies; Six New Loci; Serum Calcium Concentrations;
    Academic Unit: Faculty of Science and Engineering > Biology
    Faculty of Science and Engineering > Research Institutes > Human Health Institute
    Item ID: 17256
    Identification Number: 10.1371/journal.pgen.1003796
    Depositing User: Lorna Lopez
    Date Deposited: 29 May 2023 15:53
    Journal or Publication Title: PLoS Genetics
    Publisher: Public Library of Science
    Refereed: Yes
    Related URLs:
    URI: https://mural.maynoothuniversity.ie/id/eprint/17256
    Use Licence: This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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