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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.

SUBMITTER: Jiang X 

PROVIDER: S-EPMC5772647 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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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 X   O'Reilly Paul F PF   Aschard Hugues H   Aschard Hugues H   Hsu Yi-Hsiang YH   Richards J Brent JB   Dupuis Josée J   Ingelsson Erik E   Karasik David D   Pilz Stefan S   Berry Diane D   Kestenbaum Bryan B   Zheng Jusheng J   Luan Jianan J   Sofianopoulou Eleni E   Streeten Elizabeth A EA   Albanes Demetrius D   Lutsey Pamela L PL   Yao Lu L   Tang Weihong W   Econs Michael J MJ   Wallaschofski Henri H   Völzke Henry H   Zhou Ang A   Power Chris C   McCarthy Mark I MI   Michos Erin D ED   Boerwinkle Eric E   Weinstein Stephanie J SJ   Freedman Neal D ND   Huang Wen-Yi WY   Van Schoor Natasja M NM   van der Velde Nathalie N   Groot Lisette C P G M de LCPGM   Enneman Anke A   Cupples L Adrienne LA   Booth Sarah L SL   Vasan Ramachandran S RS   Liu Ching-Ti CT   Zhou Yanhua Y   Ripatti Samuli S   Ohlsson Claes C   Vandenput Liesbeth L   Lorentzon Mattias M   Eriksson Johan G JG   Shea M Kyla MK   Houston Denise K DK   Kritchevsky Stephen B SB   Liu Yongmei Y   Lohman Kurt K KK   Ferrucci Luigi L   Peacock Munro M   Gieger Christian C   Beekman Marian M   Slagboom Eline E   Deelen Joris J   Heemst Diana van DV   Kleber Marcus E ME   März Winfried W   de Boer Ian H IH   Wood Alexis C AC   Rotter Jerome I JI   Rich Stephen S SS   Robinson-Cohen Cassianne C   den Heijer Martin M   Jarvelin Marjo-Riitta MR   Cavadino Alana A   Joshi Peter K PK   Wilson James F JF   Hayward Caroline C   Lind Lars L   Michaëlsson Karl K   Trompet Stella S   Zillikens M Carola MC   Uitterlinden Andre G AG   Rivadeneira Fernando F   Broer Linda L   Zgaga Lina L   Campbell Harry H   Theodoratou Evropi E   Farrington Susan M SM   Timofeeva Maria M   Dunlop Malcolm G MG   Valdes Ana M AM   Tikkanen Emmi E   Lehtimäki Terho T   Lyytikäinen Leo-Pekka LP   Kähönen Mika M   Raitakari Olli T OT   Mikkilä Vera V   Ikram M Arfan MA   Sattar Naveed N   Jukema J Wouter JW   Wareham Nicholas J NJ   Langenberg Claudia C   Forouhi Nita G NG   Gundersen Thomas E TE   Khaw Kay-Tee KT   Butterworth Adam S AS   Danesh John J   Spector Timothy T   Wang Thomas J TJ   Hyppönen Elina E   Kraft Peter P   Kiel Douglas P DP  

Nature communications 20180117 1


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<sup>-9</sup> at rs801  ...[more]

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