ArticleHuman molecular genetics2016
Paternal age effects on sperm FOXK1 and KCNA7 methylation and transmission into the next generation.
Article in Human molecular genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 4 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
49 citing papers in PubMed, 4 syntheses or guidelines pooled it, 74 citations in OpenAlex.
- Pooled it
- Fertility in the aging male: a systematic review.Fertility and sterility · 2022Pooled it
- A meta-analysis of two high-risk prospective cohort studies reveals autism-specific transcriptional changes to chromatin, autoimmune, and environmental response genes in umbilical cord blood.Molecular autism · 2019Pooled it
- Association between assisted reproductive technology and the risk of autism spectrum disorders in the offspring: a meta-analysis.Scientific reports · 2017Pooled it
- Article
- Clinical Implications of Paternal Age in Assisted Reproduction: Integrating Sperm Epigenetic Evidence.Journal of clinical medicine · 2026Review
- Paternal age, de novo mutation, and age at onset among co-affected schizophrenia sib-pairs: whole-genome sequencing in multiplex families.Molecular psychiatry · 2025Article
- Exploring Differentially Methylated Genes among Preterm Birth and Full-Term Birth.Lifestyle genomics · 2025Article
- Environmental factors associated with autism spectrum disorder in Southern Europe: a systematic review.International journal of developmental disabilities · 2025Review
- Review
- Associations of paternal age with offspring under-five mortality and perinatal outcomes: a cohort study using claims data in Taiwan.BMJ public health · 2024Article
- Article
- Age-related and species-specific methylation changes in the protein-coding marmoset sperm epigenome.Aging cell · 2024Article
- Advanced Paternal Age in Focus: Unraveling Its Influence on Assisted Reproductive Technology Outcomes.Journal of clinical medicine · 2024Review
- Article
- Effects of paternal and chronological age onAging · 2023Article
- Age-associated epigenetic changes in mammalian sperm: implications for offspring health and development.Human reproduction update · 2023Review
- The methylation profile ofFrontiers in immunology · 2023Article
- Analysis and comparisons of gene expression changes in patient- derived neurons from ROHHAD, CCHS, and PWS.Frontiers in pediatrics · 2023Article
- Associations of parental reproductive age and elevated blood pressure in offspring: An observational study.Frontiers in pediatrics · 2023Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Children of older fathers carry an increased risk for developing autism and other disorders. To elucidate the underlying mechanisms, we investigated the correlation of sperm DNA methylation with paternal age and its impact on the epigenome of the offspring. Methylation levels of nine candidate genes and LINE-1 repeats were quantified by bisulfite pyrosequencing in sperm DNA of 162 donors and 191 cord blood samples of resulting children (conceived by IVF/ICSI with the same sperm samples). Four genes showed a significant negative correlation between sperm methylation and paternal age. For FOXK1 and KCNA7, the age effect on the sperm epigenome was replicated in an independent cohort of 188 sperm samples. For FOXK1, paternal age also significantly correlated with foetal cord blood (FCB) methylation. Deep bisulfite sequencing and allele-specific pyrosequencing allowed us to distinguish between maternal and paternal alleles in FCB samples with an informative SNP. FCB methylation of the paternal FOXK1 allele was negatively correlated with paternal age, whereas maternal allele was unaffected by maternal age. Since FOXK1 duplication has been associated with autism, we studied blood FOXK1 methylation in 74 children with autism and 41 age-matched controls. The FOXK1 promoter showed a trend for accelerated demethylation in the autism group. Dual luciferase reporter assay revealed that FOXK1 methylation influences gene expression. Collectively, our study demonstrates that age-related DNA methylation changes in sperm can be transmitted to the next generation and may contribute to the increased disease risk in offspring of older fathers.
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