ReviewJournal of molecular evolution2020
Antagonistic Pleiotropy in Human Disease.
Review in Journal of molecular evolution, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis 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.
The trial behind it
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
59 citing papers in PubMed, 1 synthesis or guideline pooled it, 93 citations in OpenAlex.
- Male Infertility and Neurodegenerative Diseases: A Systematic Review of Associations and Molecular Mechanisms.International journal of molecular sciences · 2026Pooled it
- Evolution ofInternational journal of molecular sciences · 2026Review
- Article
- Temporal shifts in polygenic traits track major epidemics in Western Eurasia.bioRxiv : the preprint server for biology · 2026Article
- Selection for Function in Early Life: Implications for Early-Onset Pathologies.Evolutionary applications · 2026Article
- Evolution of the MUC1 gene in eutherian mammals as an adaptation responsible for the increasing incidence of cancer in humans.Biochimica et biophysica acta. Reviews on cancer · 2026Review
- Conserved Pathways, Divergent Outcomes: A Cross-Species Genomic Perspective on the Cancer-Neurodegeneration Paradox.International journal of molecular sciences · 2026Review
- Evolutionary perspectives on endometrial cancer: antagonistic pleiotropy.Molecular & cellular oncology · 2026Review
- Genomic Structural Equation Modelling Reveals the Shared Genetic Architecture for Oral Frailty.Oral health & preventive dentistry · 2025Article
- Coevolution of cooperative lifestyles and reduced cancer prevalence in mammals.Science advances · 2025Article
- The regulation of fatty acid mobilization is extravagant rather than frugal: a perspective indicating a limitation of the thrifty genotype hypothesis.The American journal of clinical nutrition · 2025Review
- Osteoarthritis as an evolutionary legacy: Biological ageing and chondrocyte hypertrophy.Osteoarthritis and cartilage open · 2025Review
- Dual Protective Effects of Postbiotics andBiomedicines · 2025Article
- Article
- Article
- Article
- Facial Appearance and Markers of Cardiometabolic Risk in Healthy Adult Men.Archives of sexual behavior · 2025Article
- Genetic liability to sedentary behaviour and cardiovascular disease incidence in the FinnGen and HUNT cohorts.British journal of sports medicine · 2025Article
- Explanations for failures in designed and evolved systems.PNAS nexus · 2025Article
- Proximate and ultimate causes of pregnancy sickness.Evolution, medicine, and public health · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Between the 1930s and 1950s, scientists developed key principles of population genetics to try and explain the aging process. Almost a century later, these aging theories, including antagonistic pleiotropy and mutation accumulation, have been experimentally validated in animals. Although the theories have been much harder to test in humans despite research dating back to the 1970s, recent research is closing this evidence gap. Here we examine the strength of evidence for antagonistic pleiotropy in humans, one of the leading evolutionary explanations for the retention of genetic risk variation for non-communicable diseases. We discuss the analytical tools and types of data that are used to test for patterns of antagonistic pleiotropy and provide a primer of evolutionary theory on types of selection as a guide for understanding this mechanism and how it may manifest in other diseases. We find an abundance of non-experimental evidence for antagonistic pleiotropy in many diseases. In some cases, several studies have independently found corroborating evidence for this mechanism in the same or related sets of diseases including cancer and neurodegenerative diseases. Recent studies also suggest antagonistic pleiotropy may be involved in cardiovascular disease and diabetes. There are also compelling examples of disease risk variants that confer fitness benefits ranging from resistance to other diseases or survival in extreme environments. This provides increasingly strong support for the theory that antagonistic pleiotropic variants have enabled improved fitness but have been traded for higher burden of disease later in life. Future research in this field is required to better understand how this mechanism influences contemporary disease and possible consequences for their treatment.
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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 Socratic graph.