An epigenome-wide association study of sex-specific chronological ageing

Background Advanced age is associated with cognitive and physical decline and is a major risk factor for a multitude of disorders. There is also a gap in life expectancy between males and females. DNA methylation differences have been shown to be associated with both age and sex. Here, we investigat...

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Veröffentlicht in:Genome medicine Jg. 12; H. 1; S. 1 - 11
Hauptverfasser: McCartney, Daniel L., Zhang, Futao, Hillary, Robert F., Zhang, Qian, Stevenson, Anna J., Walker, Rosie M., Bermingham, Mairead L., Boutin, Thibaud, Morris, Stewart W., Campbell, Archie, Murray, Alison D., Whalley, Heather C., Porteous, David J., Hayward, Caroline, Evans, Kathryn L., Chandra, Tamir, Deary, Ian J., McIntosh, Andrew M., Yang, Jian, Visscher, Peter M., McRae, Allan F., Marioni, Riccardo E.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London BioMed Central 31.12.2019
BioMed Central Ltd
Springer Nature B.V
BMC
Schlagworte:
Adult
Age
Aged
Ageing
Aging
Aging - genetics
Analysis
Bioinformatics
Biomedical and Life Sciences
Biomedicine
Blood
Cancer Research
Chromosomes, Human, X - genetics
Cognitive ability
CpG Islands
Deoxyribonucleic acid
Disease
DNA
DNA Methylation
Epigenetics
Female
Gene Expression Regulation
Gene mapping
Generation Scotland
Genes
Genome-Wide Association Study
Genomes
Genomics
Health aspects
Human Genetics
Humans
Life expectancy
Life span
Linear Models
Male
Medicine/Public Health
Metabolomics
Methylation
Middle Aged
Mortality
Prostate cancer
Quality control
Quantitative Trait Loci
Regression analysis
Replication
Risk factors
Sex
Sex Characteristics
Sex differences
Sexual dimorphism
Software
Studies
Systems Biology
X chromosome
United Kingdom
United Kingdom > UK
Scotland
DNA methylation
Sexual dimorphism
Generation Scotland
Ageing
X chromosome
ISSN:1756-994X, 1756-994X
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Zusammenfassung:Background Advanced age is associated with cognitive and physical decline and is a major risk factor for a multitude of disorders. There is also a gap in life expectancy between males and females. DNA methylation differences have been shown to be associated with both age and sex. Here, we investigate age-by-sex differences in blood-based DNA methylation in an unrelated cohort of 2586 individuals between the ages of 18 and 87 years, with replication in a further 4450 individuals between the ages of 18 and 93 years. Methods Linear regression models were applied, with stringent genome-wide significance thresholds ( p  < 3.6 × 10 −8 ) used in both the discovery and replication data. A second, highly conservative mixed linear model method that better controls the false-positive rate was also applied, using the same genome-wide significance thresholds. Results Using the linear regression method, 52 autosomal and 597 X-linked CpG sites, mapping to 251 unique genes, replicated with concordant effect size directions in the age-by-sex interaction analysis. The site with the greatest difference mapped to GAGE10 , an X-linked gene. Here, DNA methylation levels remained stable across the male adult age range (DNA methylation by age r  = 0.02) but decreased across female adult age range (DNA methylation by age r  = − 0.61). One site (cg23722529) with a significant age-by-sex interaction also had a quantitative trait locus (rs17321482) that is a genome-wide significant variant for prostate cancer. The mixed linear model method identified 11 CpG sites associated with the age-by-sex interaction. Conclusion The majority of differences in age-associated DNA methylation trajectories between sexes are present on the X chromosome. Several of these differences occur within genes that have been implicated in sexually dimorphic traits.
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ISSN:1756-994X
1756-994X
DOI:10.1186/s13073-019-0693-z