| Title |
Evidence from case–control and longitudinal studies supports associations of genetic variation in APOE, CETP, and IL6 with human longevity
|
|---|---|
| Published in |
GeroScience, January 2012
|
| DOI | 10.1007/s11357-011-9373-7 |
| Pubmed ID | |
| Authors |
Mette Soerensen, Serena Dato, Qihua Tan, Mikael Thinggaard, Rabea Kleindorp, Marian Beekman, H. Eka D. Suchiman, Rune Jacobsen, Matt McGue, Tinna Stevnsner, Vilhelm A. Bohr, Anton J. M. de Craen, Rudi G. J. Westendorp, Stefan Schreiber, P. Eline Slagboom, Almut Nebel, James W. Vaupel, Kaare Christensen, Lene Christiansen |
| 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. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Australia | 1 | 50% |
| United Kingdom | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Scientists | 1 | 50% |
| Members of the public | 1 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 89 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Netherlands | 1 | 1% |
| Australia | 1 | 1% |
| Brazil | 1 | 1% |
| United Kingdom | 1 | 1% |
| United States | 1 | 1% |
| Unknown | 84 | 94% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 16 | 18% |
| Student > Master | 12 | 13% |
| Student > Bachelor | 9 | 10% |
| Student > Ph. D. Student | 9 | 10% |
| Other | 7 | 8% |
| Other | 23 | 26% |
| Unknown | 13 | 15% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 25 | 28% |
| Biochemistry, Genetics and Molecular Biology | 22 | 25% |
| Medicine and Dentistry | 11 | 12% |
| Psychology | 7 | 8% |
| Engineering | 2 | 2% |
| Other | 5 | 6% |
| Unknown | 17 | 19% |
Attention Score in Context
This research output has an Altmetric Attention Score of 8. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 10 May 2013.
All research outputs
#4,369,297
of 25,373,627 outputs
Outputs from GeroScience
#560
of 1,594 outputs
Outputs of similar age
#34,355
of 249,046 outputs
Outputs of similar age from GeroScience
#12
of 24 outputs
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