Epigenome-wide association of DNA methylation in whole blood with bone mineral density

Morris, John A., Tsai, Pei-Chien, Joehanes, Roby, Zeng, Jie, Trajanoska, Katerina, Soerensen, Mette, Forgetta, Vincenzo, Castillo-Fernandez, Juan Edgar, Frost, Morten, Spector, Tim D., Christensen, Kaare, Christiansen, Lene, Rivadeneira, Fernando, Tobias, Jonathan H., Evans, David M., Kiel, Douglas P., Hsu, Yi-Hsiang, Richards, J. Brent and Bell, Jordana T. (2017) Epigenome-wide association of DNA methylation in whole blood with bone mineral density. Journal of Bone and Mineral Research, . doi:10.1002/jbmr.3148

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Author Morris, John A.
Tsai, Pei-Chien
Joehanes, Roby
Zeng, Jie
Trajanoska, Katerina
Soerensen, Mette
Forgetta, Vincenzo
Castillo-Fernandez, Juan Edgar
Frost, Morten
Spector, Tim D.
Christensen, Kaare
Christiansen, Lene
Rivadeneira, Fernando
Tobias, Jonathan H.
Evans, David M.
Kiel, Douglas P.
Hsu, Yi-Hsiang
Richards, J. Brent
Bell, Jordana T.
Title Epigenome-wide association of DNA methylation in whole blood with bone mineral density
Journal name Journal of Bone and Mineral Research   Check publisher's open access policy
ISSN 1523-4681
0884-0431
Publication date 2017-04-10
Year available 2017
Sub-type Article (original research)
DOI 10.1002/jbmr.3148
Open Access Status File (Author Post-print)
Place of publication Hoboken, NJ United States
Publisher Wiley-Blackwell Publishing
Collection year 2018
Language eng
Formatted abstract
Genetic and environmental determinants of skeletal phenotypes such as bone mineral density (BMD) may converge through the epigenome, providing a tool to better understand osteoporosis pathophysiology. As the epigenetics of BMD have been largely unexplored in humans, we performed an epigenome wide association study (EWAS) of BMD. We undertook a large-scale BMD EWAS using the Infinium HumanMethylation450 array to measure site-specific DNA methylation in up to 5,515 European descent individuals (NDiscovery = 4,614, NValidation = 901). We associated methylation at multiple cytosine-phosphate-guanine (CpG) sites with dual-energy X-ray absorptiometry derived femoral neck and lumbar spine BMD. We performed sex-combined and stratified analyses, controlling for age, weight, smoking status, estimated white blood cell proportions, and random effects for relatedness and batch effects. A 5% false-discovery rate was used to identify CpGs associated with BMD. We identified one CpG-site, cg23196985, significantly associated with femoral neck BMD in 3,232 females (P = 7.9 × 10−11) and 4,614 females and males (P = 3.0 × 10−8). cg23196985 was not associated with femoral neck BMD in an additional sample of 474 females (P = 0.64) and 901 males and females (P = 0.60). Lack of strong consistent association signal indicates that among the tested probes, no large-effect epigenetic changes in whole blood associated with BMD, suggesting future epigenomic studies of musculoskeletal traits measure DNA methylation in a different tissue with extended genome coverage.
Keyword DXA
Analysis/quantitation of bone
Osteoporosis
Diseases and disorders of/related to bone
General population studies
Epidemiology
Epigenetics
Genetic research
Human association studies
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ
Additional Notes PMID:28394087

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
UQ Diamantina Institute Publications
 
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Created: Fri, 21 Apr 2017, 11:34:40 EST by Kylie Hengst on behalf of Research Strategy and Support (Medicine)