Review and meta-analysis of genetic polymorphisms associated with exceptional human longevity.
Level 3 - non-randomized controlled study
Meta-analysis of observational genetic association studies (non-randomized/case-control cohorts).
PubMed 29890178 · doi:10.1016/j.mad.2018.06.002
What was done
Meta-analyses were performed on genetic polymorphisms previously associated with exceptional longevity (defined as age 85+). Variants were included in the meta-analyses if data were available from at least three independent studies, which included two unpublished additional cohorts.
What was found
Five polymorphisms were significantly associated with exceptional longevity: ACE rs4340, APOE ε2/3/4, FOXO3A rs2802292, KLOTHO KL-VS, and IL6 rs1800795. Pooled odds ratios ranged from 0.42 (APOE ε4) to 1.45 (FOXO3A males). Effect sizes were generally modest.
Why it matters
This meta-analysis consolidates evidence that human exceptional longevity is a polygenic trait driven by multiple variants of modest effect, particularly in pathways related to cardiovascular health.
Limits
The abstract does not state the total number of included studies, total participant count, or exact confidence intervals. Results were restricted to variants evaluated in at least three independent studies, and potential confounding factors such as gender, ethnicity, and control-group selection require further investigation.
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