ArticleAging2013
Centenarians as super-controls to assess the biological relevance of genetic risk factors for common age-related diseases: a proof of principle on type 2 diabetes.
Article in Aging, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed.
- Genetic Association of Primary Angle-Closure Glaucoma and Disease Progression.Clinical & experimental ophthalmology · 2025Article
- Article
- A domain-based framework for cognitive profile identification in Parkinson's disease across diverse samples.Frontiers in neuroanatomy · 2025Article
- Genetic variation in NOTCH1 is associated with overweight and obesity in Brazilian elderly.Scientific reports · 2024Article
- Global Research on Centenarians: A Historical and Comprehensive Bibliometric Analysis from 1887 to 2023.Annals of geriatric medicine and research · 2024Article
- Age-dependent changes in the gut microbiota and serum metabolome correlate with renal function and human aging.Aging cell · 2023Article
- Association of rs3027178 polymorphism in the circadian clock gene PER1 with susceptibility to Alzheimer's disease and longevity in an Italian population.GeroScience · 2022Article
- Protective Effects of Familial Longevity Decrease With Age and Become Negligible for Centenarians.The journals of gerontology. Series A, Biological sciences and medical sciences · 2022Article
- Early downregulation of hsa-miR-144-3p in serum from drug-naïve Parkinson's disease patients.Scientific reports · 2022Article
- Careful feature selection is key in classification of Alzheimer's disease patients based on whole-genome sequencing data.NAR genomics and bioinformatics · 2021Article
- SARS CoV2 infection _The longevity study perspectives.Ageing research reviews · 2021Review
- Polygenic Risk Score of Longevity Predicts Longer Survival Across an Age Continuum.The journals of gerontology. Series A, Biological sciences and medical sciences · 2021Article
- Centenarians as Models of Resistance and Resilience to Alzheimer's Disease and Related Dementias.Advances in geriatric medicine and research · 2020Article
- Co-shared genetics and possible risk gene pathway partially explain the comorbidity of schizophrenia, major depressive disorder, type 2 diabetes, and metabolic syndrome.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2019Review
- Centenarian controls increase variant effect sizes by an average twofold in an extreme case-extreme control analysis of Alzheimer's disease.European journal of human genetics : EJHG · 2019Article
- Rare Functional Variants in Complement Genes and Anti-FH Autoantibodies-Associated aHUS.Frontiers in immunology · 2019Article
- Impact of demography and population dynamics on the genetic architecture of human longevity.Aging · 2018Article
- Article
- Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines.Frontiers in immunology · 2018Review
- Gut microbiota changes in the extreme decades of human life: a focus on centenarians.Cellular and molecular life sciences : CMLS · 2018Review
Corrections and comments
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Authors and funding
23 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genetic association studies of age-related, chronic human diseases often suffer from a lack of power to detect modest effects. Here we propose an alternative approach of including healthy centenarians as a more homogeneous and extreme control group. As a proof of principle we focused on type 2 diabetes (T2D) and assessed /genotypic associations of 31 SNPs associated with T2D, diabetes complications and metabolic diseases and SNPs of genes relevant for telomere stability and age-related diseases. We hypothesized that the frequencies of risk variants are inversely correlated with decreasing health and longevity. We performed association analyses comparing diabetic patients and non-diabetic controls followed by association analyses with extreme phenotypic groups (T2D patients with complications and centenarians). Results drew attention to rs7903146 (TCF7L2 gene) that showed a constant increase in the frequencies of risk genotype (TT) from centenarians to diabetic patients who developed macro-complications and the strongest genotypic association was detected when diabetic patients were compared to centenarians (p_value = 9.066*10⁻⁷). We conclude that robust and biologically relevant associations can be obtained when extreme phenotypes, even with a small sample size, are compared.
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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.