Meta-Analysis of Genome-Wide Association Studies Identifies Six New Loci for Serum Calcium Concentrations
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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
Bochud, Murielle
Note: Order does not necessarily reflect citation order of authors.
Published Version
https://doi.org/10.1371/journal.pgen.1003796Metadata
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O'Seaghdha, C. M., H. Wu, Q. Yang, K. Kapur, I. Guessous, A. M. Zuber, A. Köttgen, et al. 2013. “Meta-Analysis of Genome-Wide Association Studies Identifies Six New Loci for Serum Calcium Concentrations.” PLoS Genetics 9 (9): e1003796. doi:10.1371/journal.pgen.1003796. http://dx.doi.org/10.1371/journal.pgen.1003796.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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3778004/pdf/Terms of Use
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http://nrs.harvard.edu/urn-3:HUL.InstRepos:11877086
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