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

O'Seaghdha, CM; Wu, H; Yang, Q; Kapur, K; Guessous, I; Zuber, AM; Koettgen, A; Stoudmann, C; Teumer, A; Kutalik, Z; Mangino, M; Dehghan, A; Zhang, W; Eiriksdottir, G; Li, G; Tanaka, T; Portas, L; Lopez, LM; Hayward, C; Lohman, K; Matsuda, K; Padmanabhan, S; Firsov, D; Sorice, R; Ulivi, S; Brockhaus, AC; Kleber, ME; Mahajan, A; Ernst, FD; Gudnason, V; Launer, LJ; Mace, A; Boerwinckle, E; Arking, DE; Tanikawa, C; Nakamura, Y; Brown, MJ; Gaspoz, J-M; Theler, J-M; Siscovick, DS; Psaty, BM; Bergmann, S; Vollenweider, P; Vitart, V; Wright, AF; Zemunik, T; Boban, M; Kolcic, I; Navarro, P; Brown, EM; Estrada, K; Ding, J; Harris, TB; Bandinelli, S; Hernandez, D; Singleton, AB; Girotto, G; Ruggiero, D; D'Adamo, AP; Robino, A; Meitinger, T; Meisinger, C; Davies, G; Starr, JM; Chambers, JC; Boehm, BO; Winkelmann, BR; Huang, J; Murgia, F; Wild, SH; Campbell, H; Morris, AP; Franco, OH; Hofman, A; Uitterlinden, AG; Rivadeneira, F; Voelker, U; Hannemann, A; Biffar, R; Hoffmann, W; Shin, S-Y; Lescuyer, P; Henry, H; Schurmann, C; Munroe, PB; Gasparini, P; Pirastu, N; Ciullo, M; Gieger, C; Maerz, W; Lind, L; Spector, TD; Smith, AV; Rudan, I; Wilson, JF; Polasek, O; Deary, IJ; Pirastu, M; Ferrucci, L; Liu, Y; Kestenbaum, B; Kooner, JS; Witteman, JCM; Nauck, M; Kao, WHL; Wallaschofski, H; Bonny, O; Fox, CS; Bochud, M

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

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Title:	Meta-analysis of genome-wide association studies identifies six new loci for serum calcium concentrations
Authors:	O'Seaghdha, CM Wu, H Yang, Q Kapur, K Guessous, I Zuber, AM Koettgen, A Stoudmann, C Teumer, A Kutalik, Z Mangino, M Dehghan, A Zhang, W Eiriksdottir, G Li, G Tanaka, T Portas, L Lopez, LM Hayward, C Lohman, K Matsuda, K Padmanabhan, S Firsov, D Sorice, R Ulivi, S Brockhaus, AC Kleber, ME Mahajan, A Ernst, FD Gudnason, V Launer, LJ Mace, A Boerwinckle, E Arking, DE Tanikawa, C Nakamura, Y Brown, MJ Gaspoz, J-M Theler, J-M Siscovick, DS Psaty, BM Bergmann, S Vollenweider, P Vitart, V Wright, AF Zemunik, T Boban, M Kolcic, I Navarro, P Brown, EM Estrada, K Ding, J Harris, TB Bandinelli, S Hernandez, D Singleton, AB Girotto, G Ruggiero, D D'Adamo, AP Robino, A Meitinger, T Meisinger, C Davies, G Starr, JM Chambers, JC Boehm, BO Winkelmann, BR Huang, J Murgia, F Wild, SH Campbell, H Morris, AP Franco, OH Hofman, A Uitterlinden, AG Rivadeneira, F Voelker, U Hannemann, A Biffar, R Hoffmann, W Shin, S-Y Lescuyer, P Henry, H Schurmann, C Munroe, PB Gasparini, P Pirastu, N Ciullo, M Gieger, C Maerz, W Lind, L Spector, TD Smith, AV Rudan, I Wilson, JF Polasek, O Deary, IJ Pirastu, M Ferrucci, L Liu, Y Kestenbaum, B Kooner, JS Witteman, JCM Nauck, M Kao, WHL Wallaschofski, H Bonny, O Fox, CS Bochud, M
Item Type:	Journal Article
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.
Issue Date:	19-Sep-2013
Date of Acceptance:	29-Jul-2013
URI:	http://hdl.handle.net/10044/1/72542
DOI:	https://doi.org/10.1371/journal.pgen.1003796
ISSN:	1553-7390
Publisher:	Public Library of Science (PLoS)
Start Page:	1
End Page:	13
Journal / Book Title:	PLoS Genetics
Volume:	9
Issue:	9
Copyright Statement:	This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
Keywords:	Science & Technology Life Sciences & Biomedicine Genetics & Heredity IMPRINTED PHLDA2 GENE VITAMIN-D METABOLISM PARATHYROID-HORMONE PHOSPHATE HOMEOSTASIS PLACENTAL EXPRESSION UROGENITAL SYSTEM RENAL-FUNCTION MAMMARY-GLAND BIRTH-WEIGHT PLASMA Animals Bone Density Bone and Bones Calcium European Continental Ancestry Group Gene Expression Regulation Genome-Wide Association Study Homeostasis Humans Kidney Mice Polymorphism, Single Nucleotide SUNLIGHT Consortium GEFOS Consortium Bone and Bones Kidney Animals Humans Mice Calcium Gene Expression Regulation Homeostasis Bone Density Polymorphism, Single Nucleotide European Continental Ancestry Group Genome-Wide Association Study Science & Technology Life Sciences & Biomedicine Genetics & Heredity IMPRINTED PHLDA2 GENE VITAMIN-D METABOLISM PARATHYROID-HORMONE PHOSPHATE HOMEOSTASIS PLACENTAL EXPRESSION UROGENITAL SYSTEM RENAL-FUNCTION MAMMARY-GLAND BIRTH-WEIGHT PLASMA Developmental Biology 0604 Genetics
Publication Status:	Published
Article Number:	ARTN e1003796
Online Publication Date:	2013-09-19
Appears in Collections:	National Heart and Lung Institute