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

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; Ana M. Valdes; Timothy Spector

doi:10.1038/s41467-017-02662-2

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

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. EconsHenri 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, Ana M. Valdes, Timothy Spector

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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.

Original language	English
Article number	260
Pages (from-to)	1-12
Journal	Nature Communications
Volume	9
Issue number	1
Early online date	17 Jan 2018
DOIs	https://doi.org/10.1038/s41467-017-02662-2
Publication status	Published - 2018

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Jiang, X., O'Reilly, P. F., Aschard, H., Hsu, Y. H., Richards, J. B., Dupuis, J., Ingelsson, E., Karasik, D., Pilz, S., Berry, DI., Kestenbaum, B., Zheng, J., Luan, J., Sofianopoulou, E., Streeten, E. A., Albanes, D., Lutsey, P. L., Yao, L., Tang, W., ... Spector, T. (2018). Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels. Nature Communications, 9(1), 1-12. Article 260. https://doi.org/10.1038/s41467-017-02662-2

@article{43185b30df3241cc965e5e6efccda98c,

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

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.",

author = "Xia Jiang and O'Reilly, {Paul F.} and Hugues Aschard and Hsu, {Yi Hsiang} and Richards, {J. Brent} and Jos{\'e}e Dupuis and Erik Ingelsson and David Karasik and Stefan Pilz and DIane Berry and Bryan Kestenbaum and Jusheng Zheng and Jianan Luan and Eleni Sofianopoulou and Streeten, {Elizabeth A.} and Demetrius Albanes and Lutsey, {Pamela L.} and Lu Yao and Weihong Tang and Econs, {Michael J.} and Henri Wallaschofski and Henry V{\"o}lzke and Ang Zhou and Chris Power and McCarthy, {Mark I.} and Michos, {Erin D.} and Eric Boerwinkle and Weinstein, {Stephanie J.} and Freedman, {Neal D.} and Huang, {Wen Yi} and {Van Schoor}, {Natasja M.} and {Van Der Velde}, Nathalie and Groot, {Lisette C.P.G.M.De} and Anke Enneman and Cupples, {L. Adrienne} and Booth, {Sarah L.} and Vasan, {Ramachandran S.} and Liu, {Ching Ti} and Yanhua Zhou and Samuli Ripatti and Claes Ohlsson and Liesbeth Vandenput and Mattias Lorentzon and Eriksson, {Johan G.} and Shea, {M. Kyla} and Houston, {Denise K.} and Kritchevsky, {Stephen B.} and Yongmei Liu and Valdes, {Ana M.} and Timothy Spector",

year = "2018",

doi = "10.1038/s41467-017-02662-2",

language = "English",

volume = "9",

pages = "1--12",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

number = "1",

}

Jiang, X, O'Reilly, PF, Aschard, H, Hsu, YH, Richards, JB, Dupuis, J, Ingelsson, E, Karasik, D, Pilz, S, Berry, DI, Kestenbaum, B, Zheng, J, Luan, J, Sofianopoulou, E, Streeten, EA, Albanes, D, Lutsey, PL, Yao, L, Tang, W, Econs, MJ, Wallaschofski, H, Völzke, H, Zhou, A, Power, C, McCarthy, MI, Michos, ED, Boerwinkle, E, Weinstein, SJ, Freedman, ND, Huang, WY, Van Schoor, NM, Van Der Velde, N, Groot, LCPGMD, Enneman, A, Cupples, LA, Booth, SL, Vasan, RS, Liu, CT, Zhou, Y, Ripatti, S, Ohlsson, C, Vandenput, L, Lorentzon, M, Eriksson, JG, Shea, MK, Houston, DK, Kritchevsky, SB, Liu, Y, Valdes, AM & Spector, T 2018, 'Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels', Nature Communications, vol. 9, no. 1, 260, pp. 1-12. https://doi.org/10.1038/s41467-017-02662-2

TY - JOUR

T1 - Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels

AU - Jiang, Xia

AU - O'Reilly, Paul F.

AU - Aschard, Hugues

AU - Hsu, Yi Hsiang

AU - Richards, J. Brent

AU - Dupuis, Josée

AU - Ingelsson, Erik

AU - Karasik, David

AU - Pilz, Stefan

AU - Berry, DIane

AU - Kestenbaum, Bryan

AU - Zheng, Jusheng

AU - Luan, Jianan

AU - Sofianopoulou, Eleni

AU - Streeten, Elizabeth A.

AU - Albanes, Demetrius

AU - Lutsey, Pamela L.

AU - Yao, Lu

AU - Tang, Weihong

AU - Econs, Michael J.

AU - Wallaschofski, Henri

AU - Völzke, Henry

AU - Zhou, Ang

AU - Power, Chris

AU - McCarthy, Mark I.

AU - Michos, Erin D.

AU - Boerwinkle, Eric

AU - Weinstein, Stephanie J.

AU - Freedman, Neal D.

AU - Huang, Wen Yi

AU - Van Schoor, Natasja M.

AU - Van Der Velde, Nathalie

AU - Groot, Lisette C.P.G.M.De

AU - Enneman, Anke

AU - Cupples, L. Adrienne

AU - Booth, Sarah L.

AU - Vasan, Ramachandran S.

AU - Liu, Ching Ti

AU - Zhou, Yanhua

AU - Ripatti, Samuli

AU - Ohlsson, Claes

AU - Vandenput, Liesbeth

AU - Lorentzon, Mattias

AU - Eriksson, Johan G.

AU - Shea, M. Kyla

AU - Houston, Denise K.

AU - Kritchevsky, Stephen B.

AU - Liu, Yongmei

AU - Valdes, Ana M.

AU - Spector, Timothy

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

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U2 - 10.1038/s41467-017-02662-2

DO - 10.1038/s41467-017-02662-2

M3 - Article

AN - SCOPUS:85041401774

SN - 2041-1723

VL - 9

SP - 1

EP - 12

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 260

ER -

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

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