title: Genetic and Environmental Causes of Variation in the Difference Between Biological Age Based on DNA Methylation and Chronological Age for Middle-Aged Women.
abstract: The disease- and mortality-related difference between biological age based on DNA methylation and chronological age (Δage) has been found to have approximately 40% heritability by assuming that the familial correlation is only explained by additive genetic factors. We calculated two different Δage measures for 132 middle-aged female twin pairs (66 monozygotic and 66 dizygotic twin pairs) and their 215 sisters using DNA methylation data measured by the Infinium HumanMethylation450 BeadChip arrays. For each Δage measure, and their combined measure, we estimated the familial correlation for MZ, DZ and sibling pairs using the multivariate normal model for pedigree analysis. We also pooled our estimates with those from a former study to estimate weighted average correlations. For both Δage measures, there was familial correlation that varied across different types of relatives. No evidence of a difference was found between the MZ and DZ pair correlations, or between the DZ and sibling pair correlations. The only difference was between the MZ and sibling pair correlations (p < .01), and there was marginal evidence that the MZ pair correlation was greater than twice the sibling pair correlation (p < .08). For weighted average correlation, there was evidence that the MZ pair correlation was greater than the DZ pair correlation (p < .03), and marginally greater than twice the sibling pair correlation (p < .08). The varied familial correlation of Δage is not explained by additive genetic factors alone, implying the existence of shared non-genetic factors explaining variation in Δage for middle-aged women.
authors.affiliation: Centre for Epidemiology and Biostatistics,Melbourne School of Population and Global Health,The University of Melbourne,Melbourne,Victoria,Australia.
authors.forename: Shuai
authors.initials: S
authors.lastname: Li
authors.affiliation: Genetic Epidemiology Laboratory,Department of Pathology,The University of Melbourne,Melbourne,Victoria,Australia.
authors.forename: Ee Ming
authors.initials: EM
authors.lastname: Wong
authors.affiliation: Genetic Epidemiology Laboratory,Department of Pathology,The University of Melbourne,Melbourne,Victoria,Australia.
authors.forename: JiHoon E
authors.initials: JE
authors.lastname: Joo
authors.affiliation: VLSCI Life Sciences Computation Centre,The University of Melbourne,Melbourne,Victoria,Australia.
authors.forename: Chol-Hee
authors.initials: CH
authors.lastname: Jung
authors.affiliation: VLSCI Life Sciences Computation Centre,The University of Melbourne,Melbourne,Victoria,Australia.
authors.forename: Jessica
authors.initials: J
authors.lastname: Chung
authors.affiliation: Centre for Epidemiology and Biostatistics,Melbourne School of Population and Global Health,The University of Melbourne,Melbourne,Victoria,Australia.
authors.forename: Carmel
authors.initials: C
authors.lastname: Apicella
authors.affiliation: Centre for Genetic Origins of Health and Disease,The University of Western Australia,Perth,Western Australia,Australia.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Stone
authors.affiliation: Centre for Epidemiology and Biostatistics,Melbourne School of Population and Global Health,The University of Melbourne,Melbourne,Victoria,Australia.
authors.forename: Gillian S
authors.initials: GS
authors.lastname: Dite
authors.affiliation: Centre for Epidemiology and Biostatistics,Melbourne School of Population and Global Health,The University of Melbourne,Melbourne,Victoria,Australia.
authors.forename: Graham G
authors.initials: GG
authors.lastname: Giles
authors.affiliation: Genetic Epidemiology Laboratory,Department of Pathology,The University of Melbourne,Melbourne,Victoria,Australia.
authors.forename: Melissa C
authors.initials: MC
authors.lastname: Southey
authors.affiliation: Centre for Epidemiology and Biostatistics,Melbourne School of Population and Global Health,The University of Melbourne,Melbourne,Victoria,Australia.
authors.forename: John L
authors.initials: JL
authors.lastname: Hopper
mesh_terms: D000367:Age Factors; D019175:DNA Methylation; D005260:Female; D059647:Gene-Environment Interaction; D006801:Humans; D008875:Middle Aged
keywords: DNA methylation; age; familial correlation; heritability; twin family study