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An epigenome-wide association study of sex-specific chronological ageing
Open accessPublished version of a preprint
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 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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“As advanced aging is the strongest factor for AD, we also compared our results with those from Yusipov et al. [94] and McCartney et al. [35], which identified 8 and 52 autosomal CpGs differentially affected by aging, but we did not find any overlap with these previous studies.”
From Distinct sex-specific DNA methylation differences in Alzheimer’s disease (2022) · cites this paper as [35]
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Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625
limma powers differential expression analyses for RNA-sequencing and microarray studies
Ritchie, M. E., Phipson, B., Wu, D., Hu, Y., Law, C. W., Shi, W., & Smyth, G. K. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv007 · Cited by 40,458
The Molecular Signatures Database Hallmark Gene Set Collection
Liberzon, A., Birger, C., Thorvaldsdóttir, H., Ghandi, M., Mesirov, J. P., & Tamayo, P. (2015) · Cell Systems · doi:10.1016/j.cels.2015.12.004 · Cited by 13,807
DNA methylation age of human tissues and cell types
Horvath, S. (2013) · Genome Biology · doi:10.1186/gb-2013-14-10-r115 · Cited by 7,075
Genome-wide methylation profiles reveal quantitative views of human aging rates
Hannum, G., Guinney, J., Zhao, L., Zhang, L., Hughes, G., Sadda, S., Klotzle, B., Bibikova, M., Fan, J.-B., Gao, Y., et al. (2013) · Molecular Cell · doi:10.1016/j.molcel.2012.10.016 · Cited by 4,270
Functional mapping and annotation of genetic associations with FUMA
Watanabe, K., Taskesen, E., van Bochoven, A., & Posthuma, D. (2017) · Nature Communications · doi:10.1038/s41467-017-01261-5 · Cited by 4,083
Buniello, A., MacArthur, J. A. L., Cerezo, M., Harris, L. W., Hayhurst, J., Malangone, C., McMahon, A., Morales, J., Mountjoy, E., Sollis, E., et al. (2019) · Nucleic Acids Research · doi:10.1093/nar/gky1120 · Cited by 4,000
An epigenetic biomarker of aging for lifespan and healthspan
Levine, M. E., Lu, A. T., Quach, A., Chen, B. H., Assimes, T. L., Bandinelli, S., Hou, L., Baccarelli, A. A., Stewart, J. D., Li, Y., et al. (2018) · Aging · doi:10.18632/aging.101414 · Cited by 3,675
DNA methylation-based biomarkers and the epigenetic clock theory of ageing
Horvath, S., & Raj, K. (2018) · Nature Reviews Genetics · doi:10.1038/s41576-018-0004-3 · Cited by 3,095
DNA methylation GrimAge strongly predicts lifespan and healthspan
Lu, A. T., Quach, A., Wilson, J. G., Reiner, A. P., Aviv, A., Raj, K., Hou, L., Baccarelli, A. A., Li, Y., Stewart, J. D., et al. (2019) · Aging · doi:10.18632/aging.101684 · Cited by 2,540
Research works printed but not linked: 1
- R Core Team. R development Core team. R a Lang. Environ. Stat Comput 2017; 55: 275–286.
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McCartney, D. L., Min, J. L., Richmond, R. C., Lu, A. T.-H., Sobczyk, M., Davies, G., Broer, L., Guo, X., Jeong, A., Jung, J., et al. (2021) · Genome biology · doi:10.1186/s13059-021-02398-9 · Cited by 310
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Ying, K., Liu, H., Tarkhov, A. E., Sadler, M. C., Lu, A. T.-H., Moqri, M., Horvath, S., Kutalik, Z., Shen, X., & Gladyshev, V. N. (2024) · Nature Aging · doi:10.1038/s43587-023-00557-0 · Cited by 235
Olbrecht, S., Busschaert, P., Qian, J., Vanderstichele, A., Loverix, L., Gorp, T. V., Nieuwenhuysen, E. V., Han, S., den Broeck, A. V., Coosemans, A., et al. (2021) · Genome Medicine · doi:10.1186/s13073-021-00922-x · Cited by 195
Simpson, D. J., & Chandra, T. (2021) · Aging Cell · doi:10.1111/acel.13452 · Cited by 195
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Metadata
- Authors
- McCartney, D. L., Zhang, F., Hillary, R. F., Zhang, Q., Stevenson, A. J., Walker, R. M., Bermingham, M. L., Boutin, T., Morris, S. W., Campbell, A., Murray, A. D., Whalley, H. C., Porteous, D. J., Hayward, C., Evans, K. L., Chandra, T., Deary, I. J., McIntosh, A. M., Yang, J., Visscher, P. M., McRae, A. F., & Marioni, R. E.
- Affiliations
- Institute of Genetics and Cancer (GB)
- The University of Queensland (AU)
- University of Aberdeen (GB)
- Royal Edinburgh Hospital (GB)
- University of Edinburgh (GB)
- Corresponding author
- Marioni, Riccardo E.
- ORCID
- McCartney, Daniel L.
- Zhang, Futao
- Hillary, Robert F.
- Zhang, Qian
- Stevenson, Anna J.
- Walker, Rosie M.
- Bermingham, Mairead L.
- Boutin, Thibaud
- 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.
- Venue
- Genome Medicine
- Published
- 2019-12-31
- Volume
- 12
- Issue
- 1
- Pages
- 1-1
- ISSN
- 1756-994X (ISSN-L)
- PMC
- PMC6938636
- OpenAlex
- W2992920781
- Cited by
- 152
- References
- 63
- Citations by year
- 2026: 7 · 2025: 32 · 2024: 26 · 2023: 17 · 2022: 26 · 2021: 40 · 2020: 4
- FWCI
- 6.12
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Genome Medicine (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Aberdeen University Research Archive (Aberdeen University) (submittedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Wellcome Trust (104036/Z/14/Z, 108890/Z/15/Z)
- Alzheimer’s Research UK (ARUK-PG2017B-10)
- National Health and Medical Research Council (1078037, 1083656)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- DNA methylation, chronological aging, sex differences, X chromosome, epigenome-wide association study, sexually dimorphic traits, blood DNA methylation, linear mixed models
- MeSH terms
- Adult, Aged, Aging, Female, Gene Expression Regulation, Humans, Male, Middle Aged, Sex Characteristics, Linear Models, CpG Islands, DNA Methylation, Quantitative Trait Loci, Chromosomes, Human, X, Genome-Wide Association Study
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