ReviewBiogerontology2016
Puzzling role of genetic risk factors in human longevity: "risk alleles" as pro-longevity variants.
Review in Biogerontology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
41 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Strong impact of natural-selection-free heterogeneity in genetics of age-related phenotypes.Aging · 2018Pooled it
- Pleiotropic Associations of Allelic Variants in a 2q22 Region with Risks of Major Human Diseases and Mortality.PLoS genetics · 2016Pooled it
- A Data-Driven Approach for Estimating Type 2 Diabetes-Related Costs in Greece.Journal of market access & health policy · 2025Article
- SNP rs6543176 is associated with extreme human longevity but increased risk for cancer.GeroScience · 2025Article
- Biomarkers of Aging and Relevant Evaluation Techniques: A Comprehensive Review.Aging and disease · 2024Review
- Graves disease is associated with increased risk of clinical Alzheimer's disease: evidence from the Medicare system.Clinical diabetes and endocrinology · 2024Article
- Understanding the interplay between APO E polymorphism and cognition in the Italian oldest old: results from the "Mugello study".Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024Article
- More evidence for widespread antagonistic pleiotropy in polymorphic disease alleles.Frontiers in genetics · 2024Review
- Graves Disease is Associated with Increased Risk of Clinical Alzheimer's Disease: Evidence from the Medicare System.Research square · 2023Article
- Article
- The Construction of a Multidomain Risk Model of Alzheimer's Disease and Related Dementias.Journal of Alzheimer's disease : JAD · 2023Article
- Genetic trade-offs between complex diseases and longevity.Aging cell · 2022Article
- Association of rs3027178 polymorphism in the circadian clock gene PER1 with susceptibility to Alzheimer's disease and longevity in an Italian population.GeroScience · 2022Article
- "CRISPR for Disabilities: How to Self-Regulate" or Something?Journal of bioethical inquiry · 2022Article
- Review
- Interplay between stress-related genes may influence Alzheimer's disease development: The results of genetic interaction analyses of human data.Mechanisms of ageing and development · 2021Article
- SARS CoV2 infection _The longevity study perspectives.Ageing research reviews · 2021Review
- Decline in biological resilience as key manifestation of aging: Potential mechanisms and role in health and longevity.Mechanisms of ageing and development · 2021Review
- Integrated genetic analyses revealed novel human longevity loci and reduced risks of multiple diseases in a cohort study of 15,651 Chinese individuals.Aging cell · 2021Article
- Discovery and Mediation Analysis of Cross-Phenotype Associations Between Asthma and Body Mass Index in 12q13.2.American journal of epidemiology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Funding
Abstract
Complex diseases are major contributors to human mortality in old age. Paradoxically, many genetic variants that have been associated with increased risks of such diseases are found in genomes of long-lived people, and do not seem to compromise longevity. Here we argue that trade-off-like and conditional effects of genes can play central role in this phenomenon and in determining longevity. Such effects may occur as result of: (i) antagonistic influence of gene on the development of different health disorders; (ii) change in the effect of gene on vulnerability to death with age (especially, from "bad" to "good"); (iii) gene-gene interaction; and (iv) gene-environment interaction, among other factors. A review of current knowledge provides many examples of genetic factors that may increase the risk of one disease but reduce chances of developing another serious health condition, or improve survival from it. Factors that may increase risk of a major disease but attenuate manifestation of physical senescence are also discussed. Overall, available evidence suggests that the influence of a genetic variant on longevity may be negative, neutral or positive, depending on a delicate balance of the detrimental and beneficial effects of such variant on multiple health and aging related traits. This balance may change with age, internal and external environments, and depend on genetic surrounding. We conclude that trade-off-like and conditional genetic effects are very common and may result in situations when a disease "risk allele" can also be a pro-longevity variant, depending on context. We emphasize importance of considering such effects in both aging research and disease prevention.
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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.