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Meta-analysis of genome-wide association studies identifies six new Loci for serum calcium concentrations.
Tuesday,2014-04-01 11:50 America/Los_Angeles — poolea2
| Title | Meta-analysis of genome-wide association studies identifies six new Loci for serum calcium concentrations. |
| Publication Type | Journal Article |
| Year of Publication | 2013 |
| Authors | O'Seaghdha, CM, Wu, H, Yang, Q, Kapur, K, Guessous, I, Zuber, AMercier, Köttgen, 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, A Brockhaus, C, 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, APio, 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, Völker, 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, März, 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, LWH, Wallaschofski, H, Bonny, O, Fox, CS, Bochud, M |
| Corporate/Institutional Authors | SUNLIGHT Consortium, GEFOS Consortium, |
| Journal | PLoS Genet |
| Volume | 9 |
| Issue | 9 |
| Pagination | e1003796 |
| Date Published | 2013 |
| ISSN | 1553-7404 |
| Keywords | Animals, Bone and Bones, Bone Density, Calcium, European Continental Ancestry Group, Gene Expression Regulation, Genome-Wide Association Study, Homeostasis, Humans, Kidney, Mice, Polymorphism, Single Nucleotide |
| Abstract | <p>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.</p> |
| DOI | 10.1371/journal.pgen.1003796 |
| Alternate Journal | PLoS Genet. |
| PubMed ID | 24068962 |
| PubMed Central ID | PMC3778004 |
| Grant List | UL1RR025005 / RR / NCRR NIH HHS / United States N02-HL-6-4278 / HL / NHLBI NIH HHS / United States N01-HC-25195 / HC / NHLBI NIH HHS / United States UL1 RR033176 / RR / NCRR NIH HHS / United States CZB/4/710 / / Chief Scientist Office / United Kingdom 098017 / / Wellcome Trust / United Kingdom UL1RR033176 / RR / NCRR NIH HHS / United States UL1TR000124 / TR / NCATS NIH HHS / United States 081682 / / Wellcome Trust / United Kingdom R01HL59367 / HL / NHLBI NIH HHS / United States HSN268201100012C / / PHS HHS / United States HHSN268201100005C / / PHS HHS / United States HL105756 / HL / NHLBI NIH HHS / United States N01AG62101 / AG / NIA NIH HHS / United States N01- HC-75150 / HC / NHLBI NIH HHS / United States 263 MD 821336 / MD / NIMHD NIH HHS / United States AG-15928 / AG / NIA NIH HHS / United States HHSN268201100009C / / PHS HHS / United States N01-HC- 85239 / HC / NHLBI NIH HHS / United States 1R01AG032098-01A1 / AG / NIA NIH HHS / United States AG-20098 / AG / NIA NIH HHS / United States HHSN268200625226C / / PHS HHS / United States N01-AG-1-2100 / AG / NIA NIH HHS / United States HL087652 / HL / NHLBI NIH HHS / United States MR/K026992/1 / / Medical Research Council / United Kingdom N01-HC-85086 / HC / NHLBI NIH HHS / United States HHSN268201100010C / / PHS HHS / United States U01HG004402 / HG / NHGRI NIH HHS / United States AG-027058 / AG / NIA NIH HHS / United States N01-HC-35129 / HC / NHLBI NIH HHS / United States N01 HC-55222 / HC / NHLBI NIH HHS / United States HHSN268201100008C / / PHS HHS / United States 064890 / / Wellcome Trust / United Kingdom R01HL087641 / HL / NHLBI NIH HHS / United States MC_PC_U127592696 / / Medical Research Council / United Kingdom 090532 / / Wellcome Trust / United Kingdom KO3598/2-1 / / PHS HHS / United States N01 HC-15103 / HC / NHLBI NIH HHS / United States HHSN268201100007C / / PHS HHS / United States HHSN268201100011C / / PHS HHS / United States DK063491 / DK / NIDDK NIH HHS / United States N01-HC-45133 / HC / NHLBI NIH HHS / United States G0700704 / / Medical Research Council / United Kingdom N01-HC-85079 / HC / NHLBI NIH HHS / United States N01AG62103 / AG / NIA NIH HHS / United States HHSN268201200036C / / PHS HHS / United States HHSN268200782096C / / PHS HHS / United States HL080295 / HL / NHLBI NIH HHS / United States N01AG62106 / AG / NIA NIH HHS / United States BB/F019394/1 / / Biotechnology and Biological Sciences Research Council / United Kingdom MC_U127592696 / / Medical Research Council / United Kingdom AG-023629 / AG / NIA NIH HHS / United States HHSN268201100006C / / PHS HHS / United States 263 MD 9164 / MD / NIMHD NIH HHS / United States R01HL086694 / HL / NHLBI NIH HHS / United States |