Meta-analysis of genome-wide association studies identifies six new loci for serum calcium concentrations
| العنوان: | Meta-analysis of genome-wide association studies identifies six new loci for serum calcium concentrations |
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| المؤلفون: | Conall M. O'Seaghdha, 1, 2, ¶ Hongsheng Wu, 3, 4 Qiong Yang, 3 Karen Kapur, 5 Idris Guessous, 6, 7, 8, ¶ Annie Mercier Zuber, 9 Anna Köttgen, ¶ Candice Stoudmann, 9 Alexander Teumer, 12 Zoltán Kutalik, 5, 13 Massimo Mangino, 14 Abbas Dehghan, 15 Weihua Zhang, 17 Gudny Eiriksdottir, 18 Guo Li, 19 Toshiko Tanaka, 20 Laura Portas, 21 Lorna M. Lopez, 22 Caroline Hayward, 23 Kurt Lohman, 24 Koichi Matsuda, 25 Sandosh Padmanabhan, 26 Dmitri Firsov, 9 Rossella Sorice, 27 Sheila Ulivi, 28 A. Catharina Brockhaus, 30 Marcus E. Kleber, 32 Anubha Mahajan, 33 Florian D. Ernst, 12 Vilmundur Gudnason, 34 Lenore J. Launer, 35 Aurelien Mace, 13 Eric Boerwinckle, 36 Dan E. Arking, 37 Chizu Tanikawa, 25 Yusuke Nakamura, 25 Morris J. Brown, 38 Jean-Michel Gaspoz, 39 Jean-Marc Theler, 7 David S. Siscovick, 40 Bruce M. Psaty, 42 Sven Bergmann, 13 Peter Vollenweider, 43 Veronique Vitart, 23 Alan F. Wright, 23 Tatijana Zemunik, 44 Mladen Boban, 45 Ivana Kolcic, 44 Pau Navarro, 23 Edward M. Brown, 46 Karol Estrada, 47 Jingzhong Ding, 46 Tamara B. Harris, 35 Stefania Bandinelli, 48 Dena Hernandez, 49 Andrew B. Singleton, 49 Giorgia Girotto, 28 Daniela Ruggiero, 27 Adamo Pio d'Adamo, 28 Antonietta Robino, 28 Thomas Meitinger, 51 Christa Meisinger, 52 Gail Davies, 22 John M. Starr, 22 John C. Chambers, 53 Bernhard O. Boehm, 55 Bernhard R. Winkelmann, 56 Jie Huang, 57 Federico Murgia, 21 Sarah H. Wild, 58 Harry Campbell, 58 Andrew P. Morris, 33 Oscar H. Franco, 15 Albert Hofman, 15 Andre G. Uitterlinden, 47 Fernando Rivadeneira, 47 Uwe Völker, 12 Anke Hannemann, 59 Reiner Biffar, 60 Wolfgang Hoffmann, 61 So-Youn Shin, 62 Pierre Lescuyer, 63 Hughes Henry, 64 Claudia Schurmann, 12 The SUNLIGHT consortium, The GEFOS consortium, Patricia B. Munroe, 65 Paolo Gasparini, 28 Nicola Pirastu, 28 Marina Ciullo, 27 Christian Gieger, 29 Winfried März, 66 Lars Lind, 67 Tim D. Spector, 14 Albert V. Smith, 34 Igor Rudan, 58 James F. Wilson, 58 Ozren Polasek, 44 Ian J. Deary, 22 Mario Pirastu, 21 Luigi Ferrucci, 35 Yongmei Liu, 68 Bryan Kestenbaum, 69 Jaspal S. Kooner, 71 Jacqueline C. M. Witteman, 15 Matthias Nauck, 59 W. H. Linda Kao, 72 Henri Wallaschofski, ¶ Olivier Bonny, 9, ¶ Caroline S. Fox, Murielle Bochud#6 |
| المساهمون: | Abecasis, Gonçalo R., Lee Kong Chian School of Medicine (LKCMedicine), Gaspoz, Jean-Michel, Theler, Jean-Marc, Vollenweider, Peter, Huang, Jie, Lescuyer, Pierre, Epidemiology, Erasmus School of Social and Behavioural Sciences, Internal Medicine, SUNLIGHT Consortium, GEFOS Consortium, O'Seaghdha, Cm, Wu, H, Yang, Q, Kapur, K, Guessous, I, Zuber, Am, 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, 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, Jm, Theler, Jm, Siscovick, D, 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, Giorgia, Ruggiero, D, D'Adamo, ADAMO PIO, Robino, Antonietta, 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, Sy, Lescuyer, P, Henry, H, Schurmann, C, Munroe, Pb, Gasparini, Paolo, Pirastu, Nicola, 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, J, Witteman, Jc, Nauck, M, Kao, Wh, Wallaschofski, H, Bonny, O, Fox, C, Bochud, M, Sunlight, Consortium, Gefos, Consortium |
| المصدر: | PLoS Genetics 2013, ' Meta-analysis of genome-wide association studies identifies six new Loci for serum calcium concentrations ', PLoS Genetics, vol. 9, no. 9, e1003796 . https://doi.org/10.1371/journal.pgen.1003796Test PLOS genetics (2013). doi:10.1371/journal.pgen.1003796 info:cnr-pdr/source/autori:O'Seaghdha CM1, Wu H, Yang Q, Kapur K, Guessous I, Zuber AM, 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, 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 JM, Theler JM, 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, Völker U, Hannemann A, Biffar R, Hoffmann W, Shin SY, Lescuyer P, Henry H, Schurmann C; SUNLIGHT Consortium; GEFOS Consortium, 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 JC, Nauck M, Kao WH, Wallaschofski H, Bonny O, Fox CS, Bochud M./titolo:Meta-analysis of genome-wide association studies identifies six new Loci for serum calcium concentrations./doi:10.1371%2Fjournal.pgen.1003796/rivista:PLOS genetics/anno:2013/pagina_da:/pagina_a:/intervallo_pagine:/volume info:cnr-pdr/source/autori:Conall M. O'Seaghdha,1,2,¶ Hongsheng Wu,1,3,4 Qiong Yang,1,3 Karen Kapur,5 Idris Guessous,6,7,8,¶ Annie Mercier Zuber,9 Anna Köttgen,10,11,¶ Candice Stoudmann,9 Alexander Teumer,12 Zoltán Kutalik,5,13 Massimo Mangino,14 Abbas Dehghan,15 Weihua Zhang,16,17 Gudny Eiriksdottir,18 Guo Li,19 Toshiko Tanaka,20 Laura Portas,21 Lorna M. Lopez,22 Caroline Hayward,23 Kurt Lohman,24 Koichi Matsuda,25 Sandosh Padmanabhan,26 Dmitri Firsov,9 Rossella Sorice,27 Sheila Ulivi,28 A. Catharina Brockhaus,29,30 Marcus E. Kleber,31,32 Anubha Mahajan,33 Florian D. Ernst,12 Vilmundur Gudnason,18,34 Lenore J. Launer,35 Aurelien Mace,5,13 Eric Boerwinckle,36 Dan E. Arking,37 Chizu Tanikawa,25 Yusuke Nakamura,25 Morris J. Brown,38 Jean-Michel Gaspoz,39 Jean-Marc Theler,7 David S. Siscovick,19,40 Bruce M. Psaty,19,41,42 Sven Bergmann,5,13 Peter Vollenweider,43 Veronique Vitart,23 Alan F. Wright,23 Tatijana Zemunik,44 Mladen Boban,45 Ivana Kolcic,44 Pau Navarro,23 Edward M. Brown,46 Karol Estrada,47 Jingzhong Ding,46 Tamara B. Harris,35 Stefania Bandinelli,48 Dena Hernandez,49 Andrew B. Singleton,49 Giorgia Girotto,28 Daniela Ruggiero,27 Adamo Pio d'Adamo,28 Antonietta Robino,28 Thomas Meitinger,50,51 Christa Meisinger,52 Gail Davies,22 John M. Starr,22 John C. Chambers,16,17,53 Bernhard O. Boehm,54,55 Bernhard R. Winkelmann,56 Jie Huang,57 Federico Murgia,21 Sarah H. Wild,58 Harry Campbell,58 Andrew P. Morris,33 Oscar H. Franco,15 Albert Hofman,15 Andre G. Uitterlinden,47 Fernando Rivadeneira,47 Uwe Völker,12 Anke Hannemann,59 Reiner Biffar,60 Wolfgang Hoffmann,61 So-Youn Shin,62 Pierre Lescuyer,63 Hughes Henry,64 Claudia Schurmann,12 The SUNLIGHT consortium, The GEFOS consortium, Patricia B. Munroe,65 Paolo Gasparini,28 Nicola Pirastu,28 Marina Ciullo,27 Christian Gieger,29 Winfried März,32,66 Lars Lind,67 Tim D. Spector,14 Albert V. Smith,18,34 Igor Rudan,58 James F. Wilson,58 Ozren Polasek,44 Ian J. Deary,22 Mario Pirastu,21 Luigi Ferrucci,35 Yongmei Liu,68 Bryan Kestenbaum,69 Jaspal S. Kooner,16,70,71 Jacqueline C. M. Witteman,15 Matthias Nauck,59 W. H. Linda Kao,11,72 Henri Wallaschofski,59,¶ Olivier Bonny,#9,73,¶ Caroline S. Fox,#1,74,*¶ and Murielle Bochud#6,*¶/titolo:Meta-Analysis of Genome-Wide Association Studies Identifies Six New Loci for Serum Calcium Concentrations/doi:10.1371%2Fjournal.pgen.1003796/rivista:PLOS genetics/anno:2013/pagina_da:/pagina_a:/intervallo_pagine:/volume PLOS Genetics, Vol. 9, No 9 (2013) P. e1003796 PLoS Genetics (print), 9(9):e1003796. Public Library of Science PLOS GENETICS PLoS Genet. PLoS Genetics; Vol 9 PLoS Genetics, Vol 9, Iss 9, p e1003796 (2013) Plos Genetics, vol. 9, no. 9, pp. e1003796 |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Cancer Research, Medicin och hälsovetenskap, Parathyroid hormone, Genome-wide association study, calcium, genome-wide, gene, UROGENITAL SYSTEM, Kidney, Medical and Health Sciences, Mice, 0302 clinical medicine, Bone Density, GWAS, Homeostasis, Science::Medicine [DRNTU], European Continental Ancestry Group/genetics, Genetics (clinical), Genetics, Regulation of gene expression, Genetics & Heredity, 0303 health sciences, education.field_of_study, PLASMA, Calcium/blood, GEFOS Consortium, 030220 oncology & carcinogenesis, VITAMIN-D METABOLISM, Life Sciences & Biomedicine, Research Article, medicine.medical_specialty, RENAL-FUNCTION, lcsh:QH426-470, Population, PARATHYROID-HORMONE, PHOSPHATE HOMEOSTASIS, European Continental Ancestry Group, chemistry.chemical_element, Single-nucleotide polymorphism, Biology, Calcium, SUNLIGHT Consortium, Bone and Bones/metabolism, Polymorphism, Single Nucleotide, Bone and Bones, White People, 03 medical and health sciences, IMPRINTED PHLDA2 GENE, Bone Density/genetics, MAMMARY-GLAND, Internal medicine, medicine, Animals, Humans, ddc:610, PLACENTAL EXPRESSION, education, Molecular Biology, Gene, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, ddc:613, Calcium metabolism, 0604 Genetics, Science & Technology, serum calcium, Homeostasis/genetics, BIRTH-WEIGHT, lcsh:Genetics, Kidney/metabolism, Endocrinology, chemistry, Gene Expression Regulation, Developmental Biology, Genome-Wide Association Study |
| الوصف: | 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. Author Summary Calcium is vital to many biological processes and its serum concentration is tightly regulated. Family studies have shown that serum calcium is under strong genetic control. 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. We identified seven loci (six new regions) as being robustly associated with serum calcium. Three loci implicate regions involved in rare monogenic diseases including disturbances of serum calcium levels. Several of the newly identified loci harbor genes linked to the hormonal control of serum calcium. In mice experiments, we characterized the expression of these genes in gut, kidney, and bone, and explored the influence of dietary calcium intake on the expression of these genes in these organs. Our results shed new light on the genetics of calcium homeostasis and suggest a role for dietary calcium intake in bone-specific gene expression. |
| وصف الملف: | application/pdf; text |
| اللغة: | English |
| تدمد: | 1553-7390 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0e2811d7fbf3d45ccdd8d2d362457922Test http://hdl.handle.net/10220/18635Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....0e2811d7fbf3d45ccdd8d2d362457922 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15537390 |
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