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Meta-analysis of genome-wide association studies identifies six new Loci for serum calcium concentrations.

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.

SUBMITTER: O'Seaghdha CM 

PROVIDER: S-EPMC3778004 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Meta-analysis of genome-wide association studies identifies six new Loci for serum calcium concentrations.

O'Seaghdha Conall M CM   Wu Hongsheng H   Yang Qiong Q   Kapur Karen K   Guessous Idris I   Zuber Annie Mercier AM   Köttgen Anna A   Stoudmann Candice C   Teumer Alexander A   Kutalik Zoltán Z   Mangino Massimo M   Dehghan Abbas A   Zhang Weihua W   Eiriksdottir Gudny G   Li Guo G   Tanaka Toshiko T   Portas Laura L   Lopez Lorna M LM   Hayward Caroline C   Lohman Kurt K   Matsuda Koichi K   Padmanabhan Sandosh S   Firsov Dmitri D   Sorice Rossella R   Ulivi Sheila S   Brockhaus A Catharina AC   Kleber Marcus E ME   Mahajan Anubha A   Ernst Florian D FD   Gudnason Vilmundur V   Launer Lenore J LJ   Mace Aurelien A   Boerwinckle Eric E   Arking Dan E DE   Tanikawa Chizu C   Nakamura Yusuke Y   Brown Morris J MJ   Gaspoz Jean-Michel JM   Theler Jean-Marc JM   Siscovick David S DS   Psaty Bruce M BM   Bergmann Sven S   Vollenweider Peter P   Vitart Veronique V   Wright Alan F AF   Zemunik Tatijana T   Boban Mladen M   Kolcic Ivana I   Navarro Pau P   Brown Edward M EM   Estrada Karol K   Ding Jingzhong J   Harris Tamara B TB   Bandinelli Stefania S   Hernandez Dena D   Singleton Andrew B AB   Girotto Giorgia G   Ruggiero Daniela D   d'Adamo Adamo Pio AP   Robino Antonietta A   Meitinger Thomas T   Meisinger Christa C   Davies Gail G   Starr John M JM   Chambers John C JC   Boehm Bernhard O BO   Winkelmann Bernhard R BR   Huang Jie J   Murgia Federico F   Wild Sarah H SH   Campbell Harry H   Morris Andrew P AP   Franco Oscar H OH   Hofman Albert A   Uitterlinden Andre G AG   Rivadeneira Fernando F   Völker Uwe U   Hannemann Anke A   Biffar Reiner R   Hoffmann Wolfgang W   Shin So-Youn SY   Lescuyer Pierre P   Henry Hughes H   Schurmann Claudia C   Munroe Patricia B PB   Gasparini Paolo P   Pirastu Nicola N   Ciullo Marina M   Gieger Christian C   März Winfried W   Lind Lars L   Spector Tim D TD   Smith Albert V AV   Rudan Igor I   Wilson James F JF   Polasek Ozren O   Deary Ian J IJ   Pirastu Mario M   Ferrucci Luigi L   Liu Yongmei Y   Kestenbaum Bryan B   Kooner Jaspal S JS   Witteman Jacqueline C M JC   Nauck Matthias M   Kao W H Linda WH   Wallaschofski Henri H   Bonny Olivier O   Fox Caroline S CS   Bochud Murielle M  

PLoS genetics 20130919 9

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  ...[more]

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