King's College London

Research portal

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

Research output: Contribution to journalArticle

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

Original languageEnglish
JournalJournal of Bone and Mineral Research
Early online date10 Apr 2017
Accepted/In press5 Apr 2017
E-pub ahead of print10 Apr 2017


  • Manuscript_FigureLegends_Tables_Final

    Manuscript_FigureLegends_Tables_Final.docx, 108 KB, application/vnd.openxmlformats-officedocument.wordprocessingml.document

    Uploaded date:20 Apr 2017

    Version:Accepted author manuscript

King's Authors


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.

Download statistics

No data available

View graph of relations

© 2020 King's College London | Strand | London WC2R 2LS | England | United Kingdom | Tel +44 (0)20 7836 5454