Epigenome-wide Association of DNA Methylation in Whole Blood With Bone Mineral Density

John A Morris, Pei-Chien Tsai, Roby Joehanes, Jie Zheng, Katerina Trajanoska, Mette Soerensen, Vincenzo Forgetta, Juan Edgar Castillo-Fernandez, Morten Frost, Tim D Spector, Kaare Christensen, Lene Christiansen, Fernando Rivadeneira, Jonathan H Tobias, David M Evans, Douglas P Kiel, Yi-Hsiang Hsu, J Brent Richards, Jordana T Bell

Research output: Contribution to journalArticle (Academic Journal)

20 Citations (Scopus)
214 Downloads (Pure)

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 (NDiscovery = 4614, NValidation = 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 × 10−11) and 4614 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. © 2017 American Society for Bone and Mineral Research.
Original languageEnglish
Pages (from-to)1644-1650
Number of pages7
JournalJournal of Bone and Mineral Research
Volume32
Issue number8
Early online date8 May 2017
DOIs
Publication statusPublished - 9 Aug 2017

Keywords

  • Blood Cells/metabolism
  • Bone Density
  • CpG Islands
  • DNA Methylation
  • Epigenesis, Genetic
  • Female
  • Femur Neck/metabolism
  • Genome-Wide Association Study
  • Humans
  • Male
  • Twins

Fingerprint Dive into the research topics of 'Epigenome-wide Association of DNA Methylation in Whole Blood With Bone Mineral Density'. Together they form a unique fingerprint.

  • Cite this

    Morris, J. A., Tsai, P-C., Joehanes, R., Zheng, J., Trajanoska, K., Soerensen, M., Forgetta, V., Castillo-Fernandez, J. E., Frost, M., Spector, T. D., Christensen, K., Christiansen, L., Rivadeneira, F., Tobias, J. H., Evans, D. M., Kiel, D. P., Hsu, Y-H., Richards, J. B., & Bell, J. 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. https://doi.org/10.1002/jbmr.3148