Epigenome-wide Association of DNA Methylation in Whole Blood With Bone Mineral Density.
Ontology highlight
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.
SUBMITTER: Morris JA
PROVIDER: S-EPMC5615229 | biostudies-literature | 2017 Aug
REPOSITORIES: biostudies-literature
ACCESS DATA