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

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Serval ID
serval:BIB_854850FED3EF
Type
Article: article from journal or magazin.
Collection
Publications
Title
Meta-analysis of genome-wide association studies identifies six new Loci for serum calcium concentrations.
Journal
Plos Genetics
Author(s)
O'Seaghdha C.M., Wu H., Yang Q., Kapur K., Guessous I., Zuber A.M., Köttgen A., Stoudmann C., Teumer A., Kutalik Z., Mangino M., Dehghan A., Zhang W., Eiriksdottir G., Li G., Tanaka T., Portas L., Lopez L.M., Hayward C., Lohman K., Matsuda K., Padmanabhan S., Firsov D., Sorice R., Ulivi S., Brockhaus A.C., Kleber M.E., Mahajan A., Ernst F.D., Gudnason V., Launer L.J., Mace A., Boerwinckle E., Arking D.E., Tanikawa C., Nakamura Y., Brown M.J., Gaspoz J.M., Theler J.M., Siscovick D.S., Psaty B.M., Bergmann S., Vollenweider P., Vitart V., Wright A.F., Zemunik T., Boban M., Kolcic I., Navarro P., Brown E.M., Estrada K., Ding J., Harris T.B., Bandinelli S., Hernandez D., Singleton A.B., Girotto G., Ruggiero D., d'Adamo A.P., Robino A., Meitinger T., Meisinger C., Davies G., Starr J.M., Chambers J.C., Boehm B.O., Winkelmann B.R., Huang J., Murgia F., Wild S.H., Campbell H., Morris A.P., Franco O.H., Hofman A., Uitterlinden A.G., Rivadeneira F., Völker U., Hannemann A., Biffar R., Hoffmann W., Shin S.Y., Lescuyer P., Henry H., Schurmann C., Munroe P.B., Munroe P.B., Gasparini P., Pirastu N., Ciullo M., Gieger C., März W., Lind L., Spector T.D., Smith A.V., Rudan I., Wilson J.F., Polasek O., Deary I.J., Pirastu M., Ferrucci L., Liu Y., Kestenbaum B., Kooner J.S., Witteman J.C., Nauck M., Kao W.H., Wallaschofski H., Bonny O., Fox C.S., Bochud M.
Working group(s)
SUNLIGHT Consortium, GEFOS Consortium
ISSN
1553-7404 (Electronic)
ISSN-L
1553-7390
Publication state
Published
Issued date
2013
Peer-reviewed
Oui
Volume
9
Number
9
Pages
e1003796
Language
english
Notes
Publication types: Journal Article ; Meta-Analysis ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't Publication Status: ppublish
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.
Keywords
Animals, Bone Density/genetics, Bone and Bones/metabolism, Calcium/blood, European Continental Ancestry Group/genetics, Gene Expression Regulation, Genome-Wide Association Study, Homeostasis/genetics, Humans, Kidney/metabolism, Mice, Polymorphism, Single Nucleotide
Pubmed
Open Access
Yes
Create date
17/05/2016 10:53
Last modification date
20/01/2021 6:26
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