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 |
Journal | Nature Communications |
Volume | 9 |
Issue number | 1 |
DOIs | |
Publication status | Published - 1 Dec 2018 |
Cite this
- APA
- Author
- BIBTEX
- Harvard
- Standard
- RIS
- Vancouver
}
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.
In: Nature Communications, Vol. 9, No. 1, 260, 01.12.2018.Research output: Contribution to journal › Article › Academic › peer-review
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 - Lohman, Kurt K.
AU - Ferrucci, Luigi
AU - Peacock, Munro
AU - Gieger, Christian
AU - Beekman, Marian
AU - Slagboom, Eline
AU - Deelen, Joris
AU - Heemst, DIana Van
AU - Kleber, Marcus E.
AU - März, Winfried
AU - De Boer, Ian H.
AU - Wood, Alexis C.
AU - Rotter, Jerome I.
AU - Rich, Stephen S.
AU - Robinson-Cohen, Cassianne
AU - Den Heijer, Martin
AU - Jarvelin, Marjo Riitta
AU - Cavadino, Alana
AU - Joshi, Peter K.
AU - Wilson, James F.
AU - Hayward, Caroline
AU - Lind, Lars
AU - Michaëlsson, Karl
AU - Trompet, Stella
AU - Zillikens, M. Carola
AU - Uitterlinden, Andre G.
AU - Rivadeneira, Fernando
AU - Broer, Linda
AU - Zgaga, Lina
AU - Campbell, Harry
AU - Theodoratou, Evropi
AU - Farrington, Susan M.
AU - Timofeeva, Maria
AU - Dunlop, Malcolm G.
AU - Valdes, Ana M.
AU - Tikkanen, Emmi
AU - Lehtimäki, Terho
AU - Lyytikäinen, Leo Pekka
AU - Kähönen, Mika
AU - Raitakari, Olli T.
AU - Mikkilä, Vera
AU - Ikram, M. Arfan
AU - Sattar, Naveed
AU - Jukema, J. Wouter
AU - Wareham, Nicholas J.
AU - Langenberg, Claudia
AU - Forouhi, Nita G.
AU - Gundersen, Thomas E.
AU - Khaw, Kay Tee
AU - Butterworth, Adam S.
AU - Danesh, John
AU - Spector, Timothy
AU - Wang, Thomas J.
AU - Hyppönen, Elina
AU - Kraft, Peter
AU - Kiel, Douglas P.
PY - 2018/12/1
Y1 - 2018/12/1
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.
UR - http://www.scopus.com/inward/record.url?scp=85041401774&partnerID=8YFLogxK
U2 - 10.1038/s41467-017-02662-2
DO - 10.1038/s41467-017-02662-2
M3 - Article
C2 - 29343764
AN - SCOPUS:85041401774
VL - 9
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 260
ER -