Epigenetic analysis of Paget's disease of bone identifies differentially methylated loci that predict disease status

Ilhame Diboun; Sachin Wani; Stuart H Ralston; Omar Me Albagha

doi:10.7554/eLife.65715

Epigenetic analysis of Paget's disease of bone identifies differentially methylated loci that predict disease status

Ilhame Diboun, Sachin Wani, Stuart H Ralston, Omar Me Albagha

Research output: Contribution to journal › Article › peer-review

Abstract

Paget's disease of bone (PDB) is characterized by focal increases in disorganized bone remodeling. This study aims to characterize PDB-associated changes in DNA methylation profiles in patients' blood. Meta-analysis of data from the discovery and cross-validation set, each comprising 116 PDB cases and 130 controls, revealed significant differences in DNA methylation at 14 CpG sites, 4 CpG islands, and 6 gene-body regions. These loci, including two characterized as functional through expression quantitative trait-methylation analysis, were associated with functions related to osteoclast differentiation, mechanical loading, immune function, and viral infection. A multivariate classifier based on discovery samples was found to discriminate PDB cases and controls from the cross-validation with a sensitivity of 0.84, specificity of 0.81, and an area under curve of 92.8%. In conclusion, this study has shown for the first time that epigenetic factors contribute to the pathogenesis of PDB and may offer diagnostic markers for prediction of the disease.

Original language	English
Journal	eLIFE
Volume	10
DOIs	https://doi.org/10.7554/eLife.65715
Publication status	Published - 30 Apr 2021

Keywords / Materials (for Non-textual outputs)

Aged
Aged, 80 and over
Case-Control Studies
Cell Differentiation
Cohort Studies
DNA Methylation
Epigenesis, Genetic
Female
Genetic Predisposition to Disease
Humans
Male
Middle Aged
Mutation
Osteitis Deformans/genetics
Osteoclasts/cytology

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10.7554/eLife.65715Licence: Creative Commons: Attribution (CC-BY)

OA_elife-65715
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@article{80a84eef93e04affbccbf913b0af10a5,

title = "Epigenetic analysis of Paget's disease of bone identifies differentially methylated loci that predict disease status",

abstract = "Paget's disease of bone (PDB) is characterized by focal increases in disorganized bone remodeling. This study aims to characterize PDB-associated changes in DNA methylation profiles in patients' blood. Meta-analysis of data from the discovery and cross-validation set, each comprising 116 PDB cases and 130 controls, revealed significant differences in DNA methylation at 14 CpG sites, 4 CpG islands, and 6 gene-body regions. These loci, including two characterized as functional through expression quantitative trait-methylation analysis, were associated with functions related to osteoclast differentiation, mechanical loading, immune function, and viral infection. A multivariate classifier based on discovery samples was found to discriminate PDB cases and controls from the cross-validation with a sensitivity of 0.84, specificity of 0.81, and an area under curve of 92.8\%. In conclusion, this study has shown for the first time that epigenetic factors contribute to the pathogenesis of PDB and may offer diagnostic markers for prediction of the disease.",

keywords = "Aged, Aged, 80 and over, Case-Control Studies, Cell Differentiation, Cohort Studies, DNA Methylation, Epigenesis, Genetic, Female, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Mutation, Osteitis Deformans/genetics, Osteoclasts/cytology",

author = "Ilhame Diboun and Sachin Wani and Ralston, \{Stuart H\} and Albagha, \{Omar Me\}",

note = "{\textcopyright} 2021, Diboun et al.",

year = "2021",

month = apr,

day = "30",

doi = "10.7554/eLife.65715",

language = "English",

volume = "10",

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TY - JOUR

T1 - Epigenetic analysis of Paget's disease of bone identifies differentially methylated loci that predict disease status

AU - Diboun, Ilhame

AU - Wani, Sachin

AU - Ralston, Stuart H

AU - Albagha, Omar Me

PY - 2021/4/30

Y1 - 2021/4/30

N2 - Paget's disease of bone (PDB) is characterized by focal increases in disorganized bone remodeling. This study aims to characterize PDB-associated changes in DNA methylation profiles in patients' blood. Meta-analysis of data from the discovery and cross-validation set, each comprising 116 PDB cases and 130 controls, revealed significant differences in DNA methylation at 14 CpG sites, 4 CpG islands, and 6 gene-body regions. These loci, including two characterized as functional through expression quantitative trait-methylation analysis, were associated with functions related to osteoclast differentiation, mechanical loading, immune function, and viral infection. A multivariate classifier based on discovery samples was found to discriminate PDB cases and controls from the cross-validation with a sensitivity of 0.84, specificity of 0.81, and an area under curve of 92.8%. In conclusion, this study has shown for the first time that epigenetic factors contribute to the pathogenesis of PDB and may offer diagnostic markers for prediction of the disease.

AB - Paget's disease of bone (PDB) is characterized by focal increases in disorganized bone remodeling. This study aims to characterize PDB-associated changes in DNA methylation profiles in patients' blood. Meta-analysis of data from the discovery and cross-validation set, each comprising 116 PDB cases and 130 controls, revealed significant differences in DNA methylation at 14 CpG sites, 4 CpG islands, and 6 gene-body regions. These loci, including two characterized as functional through expression quantitative trait-methylation analysis, were associated with functions related to osteoclast differentiation, mechanical loading, immune function, and viral infection. A multivariate classifier based on discovery samples was found to discriminate PDB cases and controls from the cross-validation with a sensitivity of 0.84, specificity of 0.81, and an area under curve of 92.8%. In conclusion, this study has shown for the first time that epigenetic factors contribute to the pathogenesis of PDB and may offer diagnostic markers for prediction of the disease.

KW - Aged

KW - Aged, 80 and over

KW - Case-Control Studies

KW - Cell Differentiation

KW - Cohort Studies

KW - DNA Methylation

KW - Epigenesis, Genetic

KW - Female

KW - Genetic Predisposition to Disease

KW - Humans

KW - Male

KW - Middle Aged

KW - Mutation

KW - Osteitis Deformans/genetics

KW - Osteoclasts/cytology

U2 - 10.7554/eLife.65715

DO - 10.7554/eLife.65715

M3 - Article

C2 - 33929316

SN - 2050-084X

VL - 10

JO - eLIFE

JF - eLIFE

ER -

Epigenetic analysis of Paget's disease of bone identifies differentially methylated loci that predict disease status

Abstract

Keywords / Materials (for Non-textual outputs)

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