Projects per year
Abstract
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 2,586 individuals between the ages of 18 and 87 years, with replication in a further 4,450 individuals between the ages of 18 and 93 years.
Methods:
Linear regression models were applied, with stringent genome-wide significance thresholds (P<3.6x10-8) 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.
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 2,586 individuals between the ages of 18 and 87 years, with replication in a further 4,450 individuals between the ages of 18 and 93 years.
Methods:
Linear regression models were applied, with stringent genome-wide significance thresholds (P<3.6x10-8) 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.
| Original language | English |
|---|---|
| Article number | 1 |
| Journal | Genome Biology |
| Volume | 12 |
| DOIs | |
| Publication status | Published - 31 Dec 2019 |
Keywords / Materials (for Non-textual outputs)
- DNA methylation
- ageing
- sexual dimorphism
- X-chromosome
- Generation Scotland
Fingerprint
Dive into the research topics of 'An epigenome-wide association study of sex-specific chronological ageing'. Together they form a unique fingerprint.Projects
- 6 Finished
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Translational Neuroscience: Training The Next Generation Of Basic Neuroscientists To Embrace Clinical Research
Ffrench-Constant, C. (Principal Investigator), Deary, I. (Co-investigator), Kind, P. (Co-investigator), Lawrie, S. (Co-investigator), Price, D. (Co-investigator), Shipston, M. (Co-investigator) & Wardlaw, J. (Co-investigator)
1/09/17 → 31/08/23
Project: Research
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The Disconnected Mind Phase 3
Cox, S. (Principal Investigator) & Deary, I. (Co-investigator)
1/04/16 → 31/03/23
Project: Research
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Stratifying Resilience and Depression Longitudinally
McIntosh, A. (Principal Investigator), Deary, I. (Co-investigator), Evans, K. (Co-investigator), Haley, C. (Co-investigator) & Porteous, D. (Co-investigator)
1/01/15 → 30/06/21
Project: Research
Research output
- 1 Doctoral Thesis
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A multi–omics approach to understand the role of plasma proteins in cognitive ageing and dementia
Hillary, R., 2021Research output: Thesis › Doctoral Thesis
Profiles
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Riccardo Marioni
- Centre for Genomic and Experimental Medicine
- Edinburgh Neuroscience
- Institute of Genetics and Cancer - Personal Chair of Molecular Epidemiology of Ageing
- Institute of Genetics and Cancer
Person: Academic: Research Active