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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.

Authors

Xia Jiang

Paul F. O’Reilly

Hugues Aschard

Yi-Hsiang Hsu

J. Brent Richards

Josée Dupuis

Erik Ingelsson

David Karasik

Stefan Pilz

Diane Berry

Bryan Kestenbaum

Jusheng Zheng

Jianan Luan

Eleni Sofianopoulou

Elizabeth A. Streeten

Demetrius Albanes

Pamela L. Lutsey

Lu Yao

Weihong Tang

Michael J. Econs

Henri Wallaschofski

Henry Völzke

Ang Zhou

Chris Power

Mark I. McCarthy

Erin D. Michos

Eric Boerwinkle

Stephanie J. Weinstein

Neal D. Freedman

Wen-Yi Huang

Natasja M. Van Schoor

Nathalie van der Velde

Lisette C. P. G. M. de Groot

Anke Enneman

L. Adrienne Cupples

Sarah L. Booth

Ramachandran S. Vasan

Ching-Ti Liu

Yanhua Zhou

Samuli Ripatti

Claes Ohlsson

Liesbeth Vandenput

Mattias Lorentzon

Johan G. Eriksson

M. Kyla Shea

Denise K. Houston

Stephen B. Kritchevsky

Yongmei Liu

Kurt K. Lohman

Luigi Ferrucci

Munro Peacock

Christian Gieger

Marian Beekman

Eline Slagboom

Joris Deelen

Diana van Heemst

Marcus E. Kleber

Winfried März

Ian H. de Boer

Alexis C. Wood

Jerome I. Rotter

Stephen S. Rich

Cassianne Robinson-Cohen

Martin den Heijer

Marjo-Riitta Jarvelin

Alana Cavadino

Peter K. Joshi

James F. Wilson

Caroline Hayward

Lars Lind

Karl Michaëlsson

Stella Trompet

M. Carola Zillikens

Andre G. Uitterlinden

Fernando Rivadeneira

Linda Broer

Lina Zgaga

Harry Campbell

Evropi Theodoratou

Susan M. Farrington

Maria Timofeeva

Malcolm G. Dunlop

Profile Image

ANA VALDES Ana.Valdes@nottingham.ac.uk
Professor of Molecular & Genetic Epidemiology

Emmi Tikkanen

Terho Lehtimäki

Leo-Pekka Lyytikäinen

Mika Kähönen

Olli T. Raitakari

Vera Mikkilä

M. Arfan Ikram

Naveed Sattar

J. Wouter Jukema

Nicholas J. Wareham

Claudia Langenberg

Nita G. Forouhi

Thomas E. Gundersen

Kay-Tee Khaw

Adam S. Butterworth

John Danesh

Timothy Spector

Thomas J. Wang

Elina Hyppönen

Peter Kraft

Douglas P. Kiel



Abstract

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.

Citation

Jiang, X., O’Reilly, P. F., Aschard, H., Hsu, Y., Richards, J. B., Dupuis, J., …Kiel, D. 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), https://doi.org/10.1038/s41467-017-02662-2

Journal Article Type Article
Acceptance Date Dec 15, 2017
Publication Date Jan 17, 2018
Deposit Date Feb 1, 2018
Journal Nature Communications
Electronic ISSN 2041-1723
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 9
Issue 1
Article Number 260
DOI https://doi.org/10.1038/s41467-017-02662-2
Public URL http://eprints.nottingham.ac.uk/id/eprint/49483
Publisher URL https://doi.org/10.1038/s41467-017-02662-2
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0