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...

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Main Authors:	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.
Format:	Article
Published:	Nature Publishing Group 2018
Online Access:	https://eprints.nottingham.ac.uk/49483/

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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
building	Nottingham Research Data Repository
collection	Online Access
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.
first_indexed	2025-11-14T20:12:56Z
format	Article
id	nottingham-49483
institution	University of Nottingham Malaysia Campus
institution_category	Local University
last_indexed	2025-11-14T20:12:56Z
publishDate	2018
publisher	Nature Publishing Group
recordtype	eprints
repository_type	Digital Repository
spelling	nottingham-494832020-05-04T19:27:11Z https://eprints.nottingham.ac.uk/49483/ 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. 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 2018-01-17 Article PeerReviewed 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 and Kiel, Douglas P. (2018) Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels. Nature Communications, 9 (1). 260/1-260/11. ISSN 2041-1723 https://doi.org/10.1038/s41467-017-02662-2 doi:10.1038/s41467-017-02662-2 doi:10.1038/s41467-017-02662-2
spellingShingle	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
url	https://eprints.nottingham.ac.uk/49483/ https://eprints.nottingham.ac.uk/49483/ https://eprints.nottingham.ac.uk/49483/

Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels

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