Abecasis, Gonçalo and O'Seaghdha, Conall M. and Wu, Hongsheng and Yang, Qiong and Kapur, Karen and Guessous, Idris and Zuber, Annie Mercier and Köttgen, Anna and Stoudmann, Candice and Teumer, Alexander and Kutalik, Zoltán and Mangino, Massimo and Dehghan, Abbas and Zhang, Weihua and Eiriksdottir, Gudny and Li, Guo and Tanaka, Toshiko and Portas, Laura and Lopez, Lorna M. and Hayward, Caroline and Lohman, Kurt and Matsuda, Koichi and Padmanabhan, Sandosh and Firsov, Dmitri and Sorice, Rossella and Ulivi, Sheila and Brockhaus, A. Catharina and Kleber, Marcus E. and Mahajan, Anubha and Ernst, Florian D. and Gudnason, Vilmundur and Launer, Lenore J. and Mace, Aurelien and Boerwinckle, Eric and Arking, Dan E. and Tanikawa, Chizu and Nakamura, Yusuke and Brown, Morris J. and Gaspoz, Jean-Michel and Theler, Jean-Marc and Siscovick, David S. and Psaty, Bruce M. and Bergmann, Sven and Vollenweider, Peter and Vitart, Veronique and Wright, Alan F. and Zemunik, Tatijana and Boban, Mladen and Kolcic, Ivana and Navarro, Pau and Brown, Edward M. and Estrada, Karol and Ding, Jingzhong and Harris, Tamara B. and Bandinelli, Stefania and Hernandez, Dena and Singleton, Andrew B. and Girotto, Giorgia and Ruggiero, Daniela and d'Adamo, Adamo Pio and Robino, Antonietta and Meitinger, Thomas and Meisinger, Christa and Davies, Gail and Starr, John M. and Chambers, John C. and Boehm, Bernhard O. and Winkelmann, Bernhard R. and Huang, Jie and Murgia, Federico and Wild, Sarah H. and Campbell, Harry and Morris, Andrew P. and Franco, Oscar H. and Hofman, Albert and Uitterlinden, Andre G. and Rivadeneira, Fernando and Völker, Uwe and Hannemann, Anke and Biffar, Reiner and Hoffmann, Wolfgang and Shin, So–Youn and Lescuyer, Pierre and Henry, Hughes and Schurmann, Claudia and Munroe, Patricia B. and Gasparini, Paolo and Pirastu, Nicola and Ciullo, Marina and Gieger, Christian and März, Winfried and Lind, Lars and Spector, Tim D. and Smith, Albert V. and Rudan, Igor and Wilson, James F. and Polasek, Ozren and Deary, Ian J. and Pirastu, Mario and Ferrucci, Luigi and Liu, Yongmei and Kestenbaum, Bryan and Kooner, Jaspal S. and Witteman, Jacqueline C. M. and Nauck, Matthias and Kao, W. H. Linda and Wallaschofski, Henri and Bonny, Olivier and 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:	https://doi.org/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
URI:	Publisher
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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