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Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels
Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand the previous SUNLIGHT Cons...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group UK
2018
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5772647/ https://www.ncbi.nlm.nih.gov/pubmed/29343764 http://dx.doi.org/10.1038/s41467-017-02662-2 |
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| author | Jiang, Xia O’Reilly, Paul F. Aschard, Hugues Hsu, Yi-Hsiang Richards, J. Brent Dupuis, Josée Ingelsson, Erik Karasik, David Pilz, Stefan Berry, Diane Kestenbaum, Bryan Zheng, Jusheng Luan, Jianan Sofianopoulou, Eleni Streeten, Elizabeth A. Albanes, Demetrius Lutsey, Pamela L. Yao, Lu Tang, Weihong Econs, Michael J. Wallaschofski, Henri Völzke, Henry Zhou, Ang Power, Chris McCarthy, Mark I. Michos, Erin D. Boerwinkle, Eric Weinstein, Stephanie J. Freedman, Neal D. Huang, Wen-Yi Van Schoor, Natasja M. van der Velde, Nathalie Groot, Lisette C. P. G. M. de Enneman, Anke Cupples, L. Adrienne Booth, Sarah L. Vasan, Ramachandran S. Liu, Ching-Ti Zhou, Yanhua Ripatti, Samuli Ohlsson, Claes Vandenput, Liesbeth Lorentzon, Mattias Eriksson, Johan G. Shea, M. Kyla Houston, Denise K. Kritchevsky, Stephen B. Liu, Yongmei Lohman, Kurt K. Ferrucci, Luigi Peacock, Munro Gieger, Christian Beekman, Marian Slagboom, Eline Deelen, Joris Heemst, Diana van Kleber, Marcus E. März, Winfried de Boer, Ian H. Wood, Alexis C. Rotter, Jerome I. Rich, Stephen S. Robinson-Cohen, Cassianne den Heijer, Martin Jarvelin, Marjo-Riitta Cavadino, Alana Joshi, Peter K. Wilson, James F. Hayward, Caroline Lind, Lars Michaëlsson, Karl Trompet, Stella Zillikens, M. Carola Uitterlinden, Andre G. Rivadeneira, Fernando Broer, Linda Zgaga, Lina Campbell, Harry Theodoratou, Evropi Farrington, Susan M. Timofeeva, Maria Dunlop, Malcolm G. Valdes, Ana M. Tikkanen, Emmi Lehtimäki, Terho Lyytikäinen, Leo-Pekka Kähönen, Mika Raitakari, Olli T. Mikkilä, Vera Ikram, M. Arfan Sattar, Naveed Jukema, J. Wouter Wareham, Nicholas J. Langenberg, Claudia Forouhi, Nita G. Gundersen, Thomas E. Khaw, Kay-Tee Butterworth, Adam S. Danesh, John Spector, Timothy Wang, Thomas J. Hyppönen, Elina Kraft, Peter Kiel, Douglas P. |
| author_facet | Jiang, Xia O’Reilly, Paul F. Aschard, Hugues Hsu, Yi-Hsiang Richards, J. Brent Dupuis, Josée Ingelsson, Erik Karasik, David Pilz, Stefan Berry, Diane Kestenbaum, Bryan Zheng, Jusheng Luan, Jianan Sofianopoulou, Eleni Streeten, Elizabeth A. Albanes, Demetrius Lutsey, Pamela L. Yao, Lu Tang, Weihong Econs, Michael J. Wallaschofski, Henri Völzke, Henry Zhou, Ang Power, Chris McCarthy, Mark I. Michos, Erin D. Boerwinkle, Eric Weinstein, Stephanie J. Freedman, Neal D. Huang, Wen-Yi Van Schoor, Natasja M. van der Velde, Nathalie Groot, Lisette C. P. G. M. de Enneman, Anke Cupples, L. Adrienne Booth, Sarah L. Vasan, Ramachandran S. Liu, Ching-Ti Zhou, Yanhua Ripatti, Samuli Ohlsson, Claes Vandenput, Liesbeth Lorentzon, Mattias Eriksson, Johan G. Shea, M. Kyla Houston, Denise K. Kritchevsky, Stephen B. Liu, Yongmei Lohman, Kurt K. Ferrucci, Luigi Peacock, Munro Gieger, Christian Beekman, Marian Slagboom, Eline Deelen, Joris Heemst, Diana van Kleber, Marcus E. März, Winfried de Boer, Ian H. Wood, Alexis C. Rotter, Jerome I. Rich, Stephen S. Robinson-Cohen, Cassianne den Heijer, Martin Jarvelin, Marjo-Riitta Cavadino, Alana Joshi, Peter K. Wilson, James F. Hayward, Caroline Lind, Lars Michaëlsson, Karl Trompet, Stella Zillikens, M. Carola Uitterlinden, Andre G. Rivadeneira, Fernando Broer, Linda Zgaga, Lina Campbell, Harry Theodoratou, Evropi Farrington, Susan M. Timofeeva, Maria Dunlop, Malcolm G. Valdes, Ana M. Tikkanen, Emmi Lehtimäki, Terho Lyytikäinen, Leo-Pekka Kähönen, Mika Raitakari, Olli T. Mikkilä, Vera Ikram, M. Arfan Sattar, Naveed Jukema, J. Wouter Wareham, Nicholas J. Langenberg, Claudia Forouhi, Nita G. Gundersen, Thomas E. Khaw, Kay-Tee Butterworth, Adam S. Danesh, John Spector, Timothy Wang, Thomas J. Hyppönen, Elina Kraft, Peter Kiel, Douglas P. |
| author_sort | Jiang, Xia |
| collection | PubMed |
| description | Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS discovery sample size from 16,125 to 79,366 (all European descent). This larger GWAS yields two additional loci harboring genome-wide significant variants (P = 4.7×10(−9) at rs8018720 in SEC23A, and P = 1.9×10(−14) at rs10745742 in AMDHD1). The overall estimate of heritability of 25-hydroxyvitamin D serum concentrations attributable to GWAS common SNPs is 7.5%, with statistically significant loci explaining 38% of this total. Further investigation identifies signal enrichment in immune and hematopoietic tissues, and clustering with autoimmune diseases in cell-type-specific analysis. Larger studies are required to identify additional common SNPs, and to explore the role of rare or structural variants and gene–gene interactions in the heritability of circulating 25-hydroxyvitamin D levels. |
| format | Online Article Text |
| id | pubmed-5772647 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2018 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-57726472018-01-23 Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels Jiang, Xia O’Reilly, Paul F. Aschard, Hugues Hsu, Yi-Hsiang Richards, J. Brent Dupuis, Josée Ingelsson, Erik Karasik, David Pilz, Stefan Berry, Diane Kestenbaum, Bryan Zheng, Jusheng Luan, Jianan Sofianopoulou, Eleni Streeten, Elizabeth A. Albanes, Demetrius Lutsey, Pamela L. Yao, Lu Tang, Weihong Econs, Michael J. Wallaschofski, Henri Völzke, Henry Zhou, Ang Power, Chris McCarthy, Mark I. Michos, Erin D. Boerwinkle, Eric Weinstein, Stephanie J. Freedman, Neal D. Huang, Wen-Yi Van Schoor, Natasja M. van der Velde, Nathalie Groot, Lisette C. P. G. M. de Enneman, Anke Cupples, L. Adrienne Booth, Sarah L. Vasan, Ramachandran S. Liu, Ching-Ti Zhou, Yanhua Ripatti, Samuli Ohlsson, Claes Vandenput, Liesbeth Lorentzon, Mattias Eriksson, Johan G. Shea, M. Kyla Houston, Denise K. Kritchevsky, Stephen B. Liu, Yongmei Lohman, Kurt K. Ferrucci, Luigi Peacock, Munro Gieger, Christian Beekman, Marian Slagboom, Eline Deelen, Joris Heemst, Diana van Kleber, Marcus E. März, Winfried de Boer, Ian H. Wood, Alexis C. Rotter, Jerome I. Rich, Stephen S. Robinson-Cohen, Cassianne den Heijer, Martin Jarvelin, Marjo-Riitta Cavadino, Alana Joshi, Peter K. Wilson, James F. Hayward, Caroline Lind, Lars Michaëlsson, Karl Trompet, Stella Zillikens, M. Carola Uitterlinden, Andre G. Rivadeneira, Fernando Broer, Linda Zgaga, Lina Campbell, Harry Theodoratou, Evropi Farrington, Susan M. Timofeeva, Maria Dunlop, Malcolm G. Valdes, Ana M. Tikkanen, Emmi Lehtimäki, Terho Lyytikäinen, Leo-Pekka Kähönen, Mika Raitakari, Olli T. Mikkilä, Vera Ikram, M. Arfan Sattar, Naveed Jukema, J. Wouter Wareham, Nicholas J. Langenberg, Claudia Forouhi, Nita G. Gundersen, Thomas E. Khaw, Kay-Tee Butterworth, Adam S. Danesh, John Spector, Timothy Wang, Thomas J. Hyppönen, Elina Kraft, Peter Kiel, Douglas P. Nat Commun Article Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS discovery sample size from 16,125 to 79,366 (all European descent). This larger GWAS yields two additional loci harboring genome-wide significant variants (P = 4.7×10(−9) at rs8018720 in SEC23A, and P = 1.9×10(−14) at rs10745742 in AMDHD1). The overall estimate of heritability of 25-hydroxyvitamin D serum concentrations attributable to GWAS common SNPs is 7.5%, with statistically significant loci explaining 38% of this total. Further investigation identifies signal enrichment in immune and hematopoietic tissues, and clustering with autoimmune diseases in cell-type-specific analysis. Larger studies are required to identify additional common SNPs, and to explore the role of rare or structural variants and gene–gene interactions in the heritability of circulating 25-hydroxyvitamin D levels. Nature Publishing Group UK 2018-01-17 /pmc/articles/PMC5772647/ /pubmed/29343764 http://dx.doi.org/10.1038/s41467-017-02662-2 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| spellingShingle | Article Jiang, Xia O’Reilly, Paul F. Aschard, Hugues Hsu, Yi-Hsiang Richards, J. Brent Dupuis, Josée Ingelsson, Erik Karasik, David Pilz, Stefan Berry, Diane Kestenbaum, Bryan Zheng, Jusheng Luan, Jianan Sofianopoulou, Eleni Streeten, Elizabeth A. Albanes, Demetrius Lutsey, Pamela L. Yao, Lu Tang, Weihong Econs, Michael J. Wallaschofski, Henri Völzke, Henry Zhou, Ang Power, Chris McCarthy, Mark I. Michos, Erin D. Boerwinkle, Eric Weinstein, Stephanie J. Freedman, Neal D. Huang, Wen-Yi Van Schoor, Natasja M. van der Velde, Nathalie Groot, Lisette C. P. G. M. de Enneman, Anke Cupples, L. Adrienne Booth, Sarah L. Vasan, Ramachandran S. Liu, Ching-Ti Zhou, Yanhua Ripatti, Samuli Ohlsson, Claes Vandenput, Liesbeth Lorentzon, Mattias Eriksson, Johan G. Shea, M. Kyla Houston, Denise K. Kritchevsky, Stephen B. Liu, Yongmei Lohman, Kurt K. Ferrucci, Luigi Peacock, Munro Gieger, Christian Beekman, Marian Slagboom, Eline Deelen, Joris Heemst, Diana van Kleber, Marcus E. März, Winfried de Boer, Ian H. Wood, Alexis C. Rotter, Jerome I. Rich, Stephen S. Robinson-Cohen, Cassianne den Heijer, Martin Jarvelin, Marjo-Riitta Cavadino, Alana Joshi, Peter K. Wilson, James F. Hayward, Caroline Lind, Lars Michaëlsson, Karl Trompet, Stella Zillikens, M. Carola Uitterlinden, Andre G. Rivadeneira, Fernando Broer, Linda Zgaga, Lina Campbell, Harry Theodoratou, Evropi Farrington, Susan M. Timofeeva, Maria Dunlop, Malcolm G. Valdes, Ana M. Tikkanen, Emmi Lehtimäki, Terho Lyytikäinen, Leo-Pekka Kähönen, Mika Raitakari, Olli T. Mikkilä, Vera Ikram, M. Arfan Sattar, Naveed Jukema, J. Wouter Wareham, Nicholas J. Langenberg, Claudia Forouhi, Nita G. Gundersen, Thomas E. Khaw, Kay-Tee Butterworth, Adam S. Danesh, John Spector, Timothy Wang, Thomas J. Hyppönen, Elina Kraft, Peter Kiel, Douglas P. Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels |
| title | Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels |
| title_full | Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels |
| title_fullStr | Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels |
| title_full_unstemmed | Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels |
| title_short | Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels |
| title_sort | genome-wide association study in 79,366 european-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin d levels |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5772647/ https://www.ncbi.nlm.nih.gov/pubmed/29343764 http://dx.doi.org/10.1038/s41467-017-02662-2 |
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