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, 32 8: 1644-1650. 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)
Volume 32
Issue 8
Start page 1644
End page 1650
Total pages 7
Place of publication Hoboken, NJ United States
Publisher Wiley-Blackwell
Language eng
Subject 2712 Endocrinology, Diabetes and Metabolism
2732 Orthopedics and Sports Medicine
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. Because 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 5515 European-descent individuals (N= 4614, N= 901). We associated methylation at multiple cytosine-phosphate-guanine (CpG) sites with dual-energy X-ray absorptiometry (DXA)-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 3232 females (p = 7.9 × 10) and 4614 females and males (p = 3.0 × 10). 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.
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
Grant ID 102215/2/13/2
BB/I025263/1
BB/I025751/1
Institutional Status UQ
Additional Notes PMID:28394087

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