Effect of women's fertility and sexual development on epigenetic clock: Mendelian randomization study.
AAM
AFB
AFS
ANM
Epigenetic clock
Mendelian randomization
Potential causal association
Journal
Clinical epigenetics
ISSN: 1868-7083
Titre abrégé: Clin Epigenetics
Pays: Germany
ID NLM: 101516977
Informations de publication
Date de publication:
28 09 2023
28 09 2023
Historique:
received:
12
05
2023
accepted:
25
09
2023
medline:
2
10
2023
pubmed:
29
9
2023
entrez:
28
9
2023
Statut:
epublish
Résumé
In observational studies, women's fertility and sexual development traits may have implications for DNA methylation patterns, and pregnancy-related risk factors can also affect maternal DNA methylation patterns. The aim of our study is to disentangle any potential causal associations between women's fertility and sexual development traits and epigenetic clocks, as well as to search for probable mediators by using the Mendelian randomization (MR) method. Instrumental variables for exposures, mediators, and outcomes were adopted from genome-wide association studies data of European ancestry individuals. The potential causal relationship between women's fertility and sexual development traits and four epigenetic clocks were evaluated by inverse variance weighted method and verified by other two methods. Furthermore, we employed multivariable MR (MVMR) adjusting for hypertension, hyperglycemia, BMI changes, and insomnia. Then, combining the MVMR results and previous research, we performed two-step MR to explore the mediating effects of BMI, AFS, and AFB. Multiple sensitivity analyses were further performed to verify the robustness of our findings. Leveraging two-sample MR analysis, we observed statistically significant associations between earlier age at first birth (AFB) with a higher HannumAge, PhenoAge and GrimAge acceleration(β = - 0.429, 95% CI [- 0.781 to - 0.077], p = 0.017 for HannumAge; β = - 0.571, 95% CI [- 1.006 to - 0.136], p = 0.010 for PhenoAge, and β = - 1.136, 95% CI [- 1.508 to - 0.765], p = 2.03E-09 for GrimAge respectively) and age at first sexual intercourse (AFS) with a higher HannumAge and GrimAge acceleration(β = - 0.175, 95% CI [- 0.336 to - 0.014], p = 0.033 for HannumAge; β = - 0.210, 95% CI [- 0.350 to - 0.070], p = 0.003 for GrimAge, respectively). Further analyses indicated that BMI, AFB and AFS played mediator roles in the path from women's fertility and sexual development traits to epigenetic aging. Our study suggested that AFS and AFB are associated with epigenetic aging. These findings may prove valuable in informing the development of prevention strategies and interventions targeted towards women's fertility and sexual development experiences and their relationship with epigenetic aging-related diseases.
Sections du résumé
BACKGROUND AND OBJECTIVES
In observational studies, women's fertility and sexual development traits may have implications for DNA methylation patterns, and pregnancy-related risk factors can also affect maternal DNA methylation patterns. The aim of our study is to disentangle any potential causal associations between women's fertility and sexual development traits and epigenetic clocks, as well as to search for probable mediators by using the Mendelian randomization (MR) method.
METHODS
Instrumental variables for exposures, mediators, and outcomes were adopted from genome-wide association studies data of European ancestry individuals. The potential causal relationship between women's fertility and sexual development traits and four epigenetic clocks were evaluated by inverse variance weighted method and verified by other two methods. Furthermore, we employed multivariable MR (MVMR) adjusting for hypertension, hyperglycemia, BMI changes, and insomnia. Then, combining the MVMR results and previous research, we performed two-step MR to explore the mediating effects of BMI, AFS, and AFB. Multiple sensitivity analyses were further performed to verify the robustness of our findings.
RESULTS
Leveraging two-sample MR analysis, we observed statistically significant associations between earlier age at first birth (AFB) with a higher HannumAge, PhenoAge and GrimAge acceleration(β = - 0.429, 95% CI [- 0.781 to - 0.077], p = 0.017 for HannumAge; β = - 0.571, 95% CI [- 1.006 to - 0.136], p = 0.010 for PhenoAge, and β = - 1.136, 95% CI [- 1.508 to - 0.765], p = 2.03E-09 for GrimAge respectively) and age at first sexual intercourse (AFS) with a higher HannumAge and GrimAge acceleration(β = - 0.175, 95% CI [- 0.336 to - 0.014], p = 0.033 for HannumAge; β = - 0.210, 95% CI [- 0.350 to - 0.070], p = 0.003 for GrimAge, respectively). Further analyses indicated that BMI, AFB and AFS played mediator roles in the path from women's fertility and sexual development traits to epigenetic aging.
CONCLUSIONS
Our study suggested that AFS and AFB are associated with epigenetic aging. These findings may prove valuable in informing the development of prevention strategies and interventions targeted towards women's fertility and sexual development experiences and their relationship with epigenetic aging-related diseases.
Identifiants
pubmed: 37770973
doi: 10.1186/s13148-023-01572-z
pii: 10.1186/s13148-023-01572-z
pmc: PMC10540426
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
154Informations de copyright
© 2023. BioMed Central Ltd., part of Springer Nature.
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