TY - JOUR
T1 - Epigenome-wide association of DNA methylation in whole blood with bone mineral density
AU - Morris, John A
AU - Tsai, Pei-Chien
AU - Joehanes, Roby
AU - Zheng, Jie
AU - Trajanoska, Katerina
AU - Soerensen, Mette
AU - Forgetta, Vincenzo
AU - Castillo-Fernandez, Juan Edgar
AU - Frost, Morten
AU - Spector, Tim D
AU - Christensen, Kaare
AU - Christiansen, Lene
AU - Rivadeneira, Fernando
AU - Tobias, Jonathan H
AU - Evans, David M
AU - Kiel, Douglas P
AU - Hsu, Yi-Hsiang
AU - Richards, J Brent
AU - Bell, Jordana T
N1 - This article is protected by copyright. All rights reserved.
PY - 2017/4/10
Y1 - 2017/4/10
N2 - 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.
AB - 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.
U2 - 10.1002/jbmr.3148
DO - 10.1002/jbmr.3148
M3 - Article
C2 - 28394087
SN - 0884-0431
JO - Journal of Bone and Mineral Research
JF - Journal of Bone and Mineral Research
ER -