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

Article Article scientifique Article Meta-analysis of genome-wide association studies identifies six new Loci for serum calcium concentrations eng 2013 author O'Seaghdha Conall M author Guessous Idris 760565 author Köttgen Anna collaborator Gaspoz Jean-Michel 126367 collaborator Theler Jean-Marc 21917 collaborator Vollenweider Peter 724488 collaborator Huang Jie 659578 collaborator Lescuyer Pierre 0000-0001-6986-8738 562350 author Wallaschofski Henri author Bonny Olivier author Fox Caroline S. author Bochud Murielle 41043 e1003796 10.1371/journal.pgen.1003796 24068962 1553-7390 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. 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 Dewey 613 201 Institut de médecine de premier recours 22A9 false 16 Groupe Jean-Michel Gaspoz 23 PLOS genetics 9 9 8839b94d-bd11-47a9-bf10-e64e7efc1773 Article (Published version) Public O'Seaghdha CM_2013_PLoS Genet.pdf 816144 application/pdf openAccess Faculté de médecine / Section de médecine clinique / Département de santé et médecine communautaires / Institut de médecine de premier recours

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Meta-analysis of genome-wide association studies identifies six new Loci for serum calcium concentrations	PLOS genetics			2013	639	537

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