Epigenome-wide Association of DNA Methylation in Whole Blood With Bone Mineral Density
Journal of Bone and Mineral Research , Volume 32 - Issue 8 p. 1644- 1650
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.
|BONE MINERAL DENSITY, DNA METHYLATION, EPIGENETICS, EPIGENOME-WIDE ASSOCIATION STUDY (EWAS), GENETIC EPIDEMIOLOGY|
|Journal of Bone and Mineral Research|
|This work was funded by the European Commission 7th Framework Programme; grant id fp7/259679 - Integrated research on DEvelopmental determinants of Aging and Longevity (IDEAL)|
|Organisation||Department of Epidemiology|
Morris, J.A. (John A.), Tsai, P.-C. (Pei-Chien), Joehanes, R, Zheng, J, Trajanoska, K, Soerensen, M. (Mette), … Bell, J.T. (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