ArticleAge (Dordrecht, Netherlands)2013
Gene set analysis of GWAS data for human longevity highlights the relevance of the insulin/IGF-1 signaling and telomere maintenance pathways.
Article in Age (Dordrecht, Netherlands), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 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
66 citing papers in PubMed, 2 syntheses or guidelines pooled it, 126 citations in OpenAlex.
- Meta-analysis of telomere length in 19,713 subjects reveals high heritability, stronger maternal inheritance and a paternal age effect.European journal of human genetics : EJHG · 2013Pooled it
- Systematic testing of literature reported genetic variation associated with coronary restenosis: results of the GENDER Study.PloS one · 2012Pooled it
- Genetic associations with longevity in a Calabrian cohort: an exploratory genome-wide study.GeroScience · 2026Article
- Association of the endosomal sorting processes cargo selection and membrane tubulation with human reward system reactivity.European archives of psychiatry and clinical neuroscience · 2026Article
- Endocrine Adaptations to Prolonged Fasting: From Physiology, Clinical Uncertainties, Translational Challenges to Healthspan Implications.Nutrients · 2025Review
- Review
- The Telomere-Telomerase System Is Detrimental to Health at High-Altitude.International journal of environmental research and public health · 2023Article
- Convergent genomics of longevity in rockfishes highlights the genetics of human life span variation.Science advances · 2023Article
- Insulin-like growth factors and aging: lessons from Laron syndrome.Frontiers in endocrinology · 2023Review
- Insulin and aging - a disappointing relationship.Frontiers in endocrinology · 2023Review
- Sirtuins and redox signaling interplay in neurogenesis, neurodegenerative diseases, and neural cell reprogramming.Frontiers in neuroscience · 2023Review
- Comparative epigenomics reveals the impact of ruminant-specific regulatory elements on complex traits.BMC biology · 2022Article
- Article
- MicroRNA 132-3p Is Upregulated in Laron Syndrome Patients and Controls Longevity Gene Expression.International journal of molecular sciences · 2021Article
- Predicting physiological aging rates from a range of quantitative traits using machine learning.Aging · 2021Article
- Review
- Rare genetic coding variants associated with human longevity and protection against age-related diseases.Nature aging · 2021Article
- Lifestyle's influence on community-dwelling older adults' health: A mixed-methods study design.Contemporary clinical trials communications · 2021Article
- 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
- Decline in biological resilience as key manifestation of aging: Potential mechanisms and role in health and longevity.Mechanisms of ageing and development · 2021Review
6 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In genome-wide association studies (GWAS) of complex traits, single SNP analysis is still the most applied approach. However, the identified SNPs have small effects and provide limited biological insight. A more appropriate approach to interpret GWAS data of complex traits is to analyze the combined effect of a SNP set grouped per pathway or gene region. We used this approach to study the joint effect on human longevity of genetic variation in two candidate pathways, the insulin/insulin-like growth factor (IGF-1) signaling (IIS) pathway and the telomere maintenance (TM) pathway. For the analyses, we used genotyped GWAS data of 403 unrelated nonagenarians from long-lived sibships collected in the Leiden Longevity Study and 1,670 younger population controls. We analyzed 1,021 SNPs in 68 IIS pathway genes and 88 SNPs in 13 TM pathway genes using four self-contained pathway tests (PLINK set-based test, Global test, GRASS and SNP ratio test). Although we observed small differences between the results of the different pathway tests, they showed consistent significant association of the IIS and TM pathway SNP sets with longevity. Analysis of gene SNP sets from these pathways indicates that the association of the IIS pathway is scattered over several genes (AKT1, AKT3, FOXO4, IGF2, INS, PIK3CA, SGK, SGK2, and YWHAG), while the association of the TM pathway seems to be mainly determined by one gene (POT1). In conclusion, this study shows that genetic variation in genes involved in the IIS and TM pathways is associated with human longevity.
Indexed as
Identifiers
What OpenQuestion holds
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.