ArticleClinical epigenetics2023
Effect of women's fertility and sexual development on epigenetic clock: Mendelian randomization study.
Article in Clinical epigenetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Causal validation of the relationship between 35 blood and urine biomarkers and hyperthyroidism: a bidirectional Mendelian randomization study and meta-analysis.Frontiers in endocrinology · 2024Pooled it
- Exploring the exposome and unexplained variance in biological ageing - insights from a longitudinal twin study in adolescence and early adulthood.medRxiv : the preprint server for health sciences · 2026Article
- Advances in multi-omics and aging clock research for female reproductive health and aging.MedScience · 2026Review
- Association of female reproductive traits with altered aging trajectories: Insights from genetic and observational analyses.Cell reports. Medicine · 2025Observational
- Multi-Omic Associations of Epigenetic Age Acceleration Are Heterogeneously Shaped by Genetic and Environmental Influences.Aging cell · 2025Article
- 3-Hydroxybutyrate, a metabolite in sustaining neuronal cell vitality: a mendelian randomization and in vitro experimentation.Nutrition & metabolism · 2025Article
- Examining Health Behaviors as Mechanisms Linking Earlier Pubertal Timing with Accelerated Epigenetic Aging in Late Adolescence.Journal of youth and adolescence · 2025Article
- DNA methylation-based age prediction and sex-specific epigenetic aging in a lizard with female-biased longevity.Science advances · 2025Article
- The Effect of Epigenetic Age Acceleration on Atopic Dermatitis: A Mendelian Randomization Study.Clinical, cosmetic and investigational dermatology · 2025Article
- The Impact of Age at First Sexual Intercourse on Female Reproductive Disorders: A Mendelian Randomized Study.International journal of women's health · 2025Article
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesIn 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.
methodsInstrumental 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.
resultsLeveraging 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.
conclusionsOur 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.
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