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- Title
Epigenome-wide Association of DNA Methylation in Whole Blood With Bone Mineral Density.
- Authors
Morris, John A; Tsai, Pei-Chien; Joehanes, Roby; Zheng, 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
- Abstract
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.
- Subjects
DNA methylation; BONE density; GENETIC epidemiology
- Publication
Journal of Bone & Mineral Research, 2017, Vol 32, Issue 8, p1644
- ISSN
0884-0431
- Publication type
Article
- DOI
10.1002/jbmr.3148