ReviewThe American journal of psychiatry2013
"Selfish spermatogonial selection": a novel mechanism for the association between advanced paternal age and neurodevelopmental disorders.
Review in The American journal of psychiatry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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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Who cites it
45 citing papers in PubMed, 96 citations in OpenAlex.
- Parental age and age gap in relation to neonatal health: a cohort study in eastern China.Frontiers in reproductive health · 2026Article
- Schizophrenia.Nature reviews. Disease primers · 2025Review
- Paternal age, de novo mutation, and age at onset among co-affected schizophrenia sib-pairs: whole-genome sequencing in multiplex families.Molecular psychiatry · 2025Article
- Germline mosaicism in TCF20-associated neurodevelopmental disorders: a case study and literature review.Journal of human genetics · 2025Review
- Article
- Genetic variation across and within individuals.Nature reviews. Genetics · 2024Review
- Reproductive Ageing: Current insights and a potential role of NAD in the reproductive health of aging fathers and their children.Reproduction (Cambridge, England) · 2024Review
- Male reproductive ageing: a radical road to ruin.Human reproduction (Oxford, England) · 2023Article
- Exome sequencing for structurally normal fetuses-yields and ethical issues.European journal of human genetics : EJHG · 2023Article
- The impact of paternal age on new mutations and disease in the next generation.Fertility and sterility · 2022Review
- Reproductive axis ageing and fertility in men.Reviews in endocrine & metabolic disorders · 2022Review
- Paternal age and 13 psychiatric disorders in the offspring: a population-based cohort study of 7 million children in Taiwan.Molecular psychiatry · 2022Article
- A multifactorial model for the etiology of neuropsychiatric disorders: the role of advanced paternal age.Pediatric research · 2022Review
- Non-neutral clonal selection and its potential role in mammalian germline stem cell dysfunction with advancing age.Frontiers in cell and developmental biology · 2022Review
- Characterization of SETD1A haploinsufficiency in humans and Drosophila defines a novel neurodevelopmental syndrome.Molecular psychiatry · 2021Article
- Association between paternal age and risk of schizophrenia: a nationwide population-based study.Journal of assisted reproduction and genetics · 2021Article
- Paternal age in rhesus macaques is positively associated with germline mutation accumulation but not with measures of offspring sociability.Genome research · 2020Article
- Variant recurrence in neurodevelopmental disorders: the use of publicly available genomic data identifies clinically relevant pathogenic missense variants.Genetics in medicine : official journal of the American College of Medical Genetics · 2019Article
- Selfish mutations dysregulating RAS-MAPK signaling are pervasive in aged human testes.Genome research · 2018Article
- Open niche regulation of mouse spermatogenic stem cells.Development, growth & differentiation · 2018Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
There is robust evidence from epidemiological studies that the offspring of older fathers have an increased risk of neurodevelopmental disorders, such as schizophrenia and autism. The authors present a novel mechanism that may contribute to this association. Because the male germ cell undergoes many more cell divisions across the reproductive age range, copy errors taking place in the paternal germline are associated with de novo mutations in the offspring of older men. Recently it has been recognized that somatic mutations in male germ cells that modify proliferation through dysregulation of the RAS protein pathway can lead to within-testis expansion of mutant clonal lines. First identified in association with rare disorders related to paternal age (e.g., Apert syndrome, achondroplasia), this process is known as "selfish spermatogonial selection." This mechanism favors propagation of germ cells carrying pathogenic mutations, increasingly skews the mutational profile of sperm as men age, and enriches de novo mutations in the offspring of older fathers that preferentially affect specific cellular signaling pathways. This mechanism not only offers a parsimonious explanation for the association between advanced paternal age and various neurodevelopmental disorders but also provides insights into the genetic architecture (role of de novo mutations), neurobiological correlates (altered cell cycle), and some epidemiological features of these disorders. The authors outline hypotheses to test this model. Given the secular changes for delayed parenthood in most societies, this hypothesis has important public health implications.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.