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

by Siscovick, David S. , Psaty, Bruce M. , Gudnason, Vilmundur , Guessous, Idris , Lohman, Kurt , Yang, Qiong , d'Adamo, Adamo Pio , Pirastu, Mario , Nakamura, Yusuke , Zemunik, Tatijana , Singleton, Andrew B. , Liu, Yongmei , Ernst, Florian D. , Rudan, Igor , Eiriksdottir, Gudny , Gasparini, Paolo , Boehm, Bernhard O. , Matsuda, Koichi , Robino, Antonietta , Uitterlinden, Andre G. , Vollenweider, Peter , Munroe, Patricia B. , Zuber, Annie Mercier , Girotto, Giorgia , Theler, Jean-Marc , Brockhaus, A. Catharina , Navarro, Pau , Hayward, Caroline , Ruggiero, Daniela , Estrada, Karol , Campbell, Harry , Boerwinckle, Eric , Davies, Gail , Henry, Hughes , Dehghan, Abbas , Lind, Lars , Köttgen, Anna , Sorice, Rossella , Gieger, Christian , Ferrucci, Luigi , Kapur, Karen , Spector, Tim D. , Hannemann, Anke , Ding, Jingzhong , Meisinger, Christa , Franco, Oscar H. , Ulivi, Sheila , Wright, Alan F. , Smith, Albert V. , Portas, Laura , Chambers, John C. , Lopez, Lorna M. , Polasek, Ozren , Morris, Andrew P. , Starr, John M. , Schurmann, Claudia , März, Winfried , Rivadeneira, Fernando , Völker, Uwe , Brown, Edward M. , Tanaka, Toshiko , Kolcic, Ivana , Murgia, Federico , Arking, Dan

in Animals / Bone and Bones - metabolism / Bone density / Bone Density - genetics / Calcium / Calcium - blood / Calcium, Dietary / Experiments / Gene expression / Gene Expression Regulation / Genetic aspects / Genome-wide association studies / Genome-Wide Association Study / Genomes / Homeostasis / Homeostasis - genetics / Humans / Kidney - metabolism / Kinases / Meta-analysis / Mice / Ontology / Physiological aspects / Polymorphism, Single Nucleotide / Population / White People - genetics

2013

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

2013

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

2013

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Journal Article

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

Siscovick, David S.,

Psaty, Bruce M.,

Gudnason, Vilmundur,

Guessous, Idris,

Lohman, Kurt,

Yang, Qiong,

d'Adamo, Adamo Pio,

Pirastu, Mario,

Nakamura, Yusuke,

Zemunik, Tatijana,

Singleton, Andrew B.,

Liu, Yongmei,

Ernst, Florian D.,

Rudan, Igor,

Eiriksdottir, Gudny,

Gasparini, Paolo,

Boehm, Bernhard O.,

Matsuda, Koichi,

Robino, Antonietta,

Uitterlinden, Andre G.,

Vollenweider, Peter,

Munroe, Patricia B.,

Zuber, Annie Mercier,

Girotto, Giorgia,

Theler, Jean-Marc,

Brockhaus, A. Catharina,

Navarro, Pau,

Hayward, Caroline,

Ruggiero, Daniela,

Estrada, Karol,

Campbell, Harry,

Boerwinckle, Eric,

Davies, Gail,

Henry, Hughes,

Dehghan, Abbas,

Lind, Lars,

Köttgen, Anna,

Sorice, Rossella,

Gieger, Christian,

Ferrucci, Luigi,

Kapur, Karen,

Spector, Tim D.,

Hannemann, Anke,

Ding, Jingzhong,

Meisinger, Christa,

Franco, Oscar H.,

Ulivi, Sheila,

Wright, Alan F.,

Smith, Albert V.,

Portas, Laura,

Chambers, John C.,

Lopez, Lorna M.,

Polasek, Ozren,

Morris, Andrew P.,

Starr, John M.,

Schurmann, Claudia,

März, Winfried,

Rivadeneira, Fernando,

Völker, Uwe,

Brown, Edward M.,

Tanaka, Toshiko,

Kolcic, Ivana,

Murgia, Federico,

Arking, Dan

2013

Overview

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.

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Publisher

Public Library of Science,Public Library of Science (PLoS)

Subject

Animals

/ Bone and Bones - metabolism

/ Bone density

/ Bone Density - genetics

/ Calcium

/ Calcium - blood

/ Calcium, Dietary