ArticleAge (Dordrecht, Netherlands)2013
Evidence from case-control and longitudinal studies supports associations of genetic variation in APOE, CETP, and IL6 with human longevity.
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 51 papers, 2 of them syntheses that pooled it.
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Who cites it
51 citing papers in PubMed, 2 syntheses or guidelines pooled it, 94 citations in OpenAlex.
- A Prospective Analysis of Genetic Variants Associated with Human Lifespan.G3 (Bethesda, Md.) · 2019Pooled it
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- Exploring the association of interleukin polymorphisms with aggression and internalizing behaviors in children and adolescents.Brain and behavior · 2022Article
- Single nucleotide polymorphisms located in TNFA, IL1RN, IL6R, and IL6 genes are associated with COVID-19 risk and severity in an Iranian population.Cell biology international · 2022Article
- Genes and Longevity of Lifespan.International journal of molecular sciences · 2022Review
- Measuring heritable contributions to Alzheimer's disease: polygenic risk score analysis with twins.Brain communications · 2022Article
- Machine learning methods applied to genotyping data capture interactions between single nucleotide variants in late onset Alzheimer's disease.Alzheimer's & dementia (Amsterdam, Netherlands) · 2022Article
- Exploring New Kingdoms: The Role of Extracellular Vesicles in Oxi-Inflamm-Aging Related to Cardiorenal Syndrome.Antioxidants (Basel, Switzerland) · 2021Review
- Sirtuin 6: linking longevity with genome and epigenome stability.Trends in cell biology · 2021Review
- GWAS-Top Polymorphisms Associated With Late-Onset Alzheimer Disease in Brazil: Pointing Out Possible New Culprits Among Non-Coding RNAs.Frontiers in molecular biosciences · 2021Article
- Vascular Aging in the Invertebrate Chordate,Frontiers in molecular biosciences · 2021Article
- A Long-Read Sequencing Approach for Direct Haplotype Phasing in Clinical Settings.International journal of molecular sciences · 2020Article
- Apolipoprotein E ε4 and cognitive function after surgery in middle-aged and elderly Danish twins.European journal of anaesthesiology · 2020Article
- The human immunosenescence phenotype: does it exist?Seminars in immunopathology · 2020Review
- Longevity: Lesson from Model Organisms.Genes · 2019Review
- Genetic and epigenetic regulation of human aging and longevity.Biochimica et biophysica acta. Molecular basis of disease · 2019Review
Corrections and comments
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Authors and funding
19 authors at 7 institutions in 3 countries.
Funding
Abstract
In this study, we investigated 102 single-nucleotide polymorphisms (SNPs) covering the common genetic variation in 16 genes recurrently regarded as candidates for human longevity: APOE; ACE; CETP; HFE; IL6; IL6R; MTHFR; TGFB1; APOA4; APOC3; SIRTs 1, 3, 6; and HSPAs 1A, 1L, 14. In a case-control study of 1,089 oldest-old (ages 92-93) and 736 middle-aged Danes, the minor allele frequency (MAF) of rs769449 (APOE) was significantly decreased in the oldest-old, while the MAF of rs9923854 (CETP) was significantly enriched. These effects were supported when investigating 1,613 oldest-old (ages 95-110) and 1,104 middle-aged Germans. rs769449 was in modest linkage equilibrium (R (2)=0.55) with rs429358 of the APOE-ε4 haplotype and adjusting for rs429358 eliminated the association of rs769449, indicating that the association likely reflects the well-known effect of rs429358. Gene-based analysis confirmed the effects of variation in APOE and CETP and furthermore pointed to HSPA14 as a longevity gene. In a longitudinal study with 11 years of follow-up on survival in the oldest-old Danes, only one SNP, rs2069827 (IL6), was borderline significantly associated with survival from age 92 (P-corrected=0.064). This advantageous effect of the minor allele was supported when investigating a Dutch longitudinal cohort (N=563) of oldest-old (age 85+). Since rs2069827 was located in a putative transcription factor binding site, quantitative RNA expression studies were conducted. However, no difference in IL6 expression was observed between rs2069827 genotype groups. In conclusion, we here support and expand the evidence suggesting that genetic variation in APOE, CETP, and IL6, and possible HSPA14, is associated with human longevity.
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