Review and meta-analysis of genetic polymorphisms associated with exceptional human longevity.

Mary Revelas, Anbupalam Thalamuthu, Christopher Oldmeadow, Tiffany-Jane Evans, Nicola J Armstrong, John B Kwok, Henry Brodaty, Peter R Schofield, Rodney J Scott, Perminder S Sachdev, John R Attia, Karen A Mather

Journal: Mechanisms of ageing and development 2018;175():24-34

PMID: 29890178

Full Text on Elsevier Science View on PubMed

Abstract

BACKGROUND

Many factors contribute to exceptional longevity, with genetics playing a significant role. However, to date, genetic studies examining exceptional longevity have been inconclusive. This comprehensive review seeks to determine the genetic variants associated with exceptional longevity by undertaking meta-analyses.

METHODS

Meta-analyses of genetic polymorphisms previously associated with exceptional longevity (85+) were undertaken. For each variant, meta-analyses were performed if there were data from at least three independent studies available, including two unpublished additional cohorts.

RESULTS

Five polymorphisms, ACE rs4340, APOE ε2/3/4, FOXO3A rs2802292, KLOTHO KL-VS and IL6 rs1800795 were significantly associated with exceptional longevity, with the pooled effect sizes (odds ratios) ranging from 0.42 (APOE ε4) to 1.45 (FOXO3A males).

CONCLUSION

In general, the observed modest effect sizes of the significant variants suggest many genes of small influence play a role in exceptional longevity, which is consistent with results for other polygenic traits. Our results also suggest that genes related to cardiovascular health may be implicated in exceptional longevity. Future studies should examine the roles of gender and ethnicity and carefully consider study design, including the selection of appropriate controls.

Address: Centre for Healthy Brain Ageing, School of Psychiatry, UNSW Medicine, University of New South Wales, Sydney, Australia.; Hunter Medical Research Institute, Newcastle, Australia.; Centre for Healthy Brain Ageing, School of Psychiatry, UNSW Medicine, University of New South Wales, Sydney, Australia; Mathematics and Statistics, Murdoch University, Perth, Australia.; Neuroscience Research Australia, Randwick, Australia; School of Medical Sciences, University of New South Wales, Sydney, Australia.; Centre for Healthy Brain Ageing, School of Psychiatry, UNSW Medicine, University of New South Wales, Sydney, Australia; Dementia Centre for Research Collaboration, University of New South Wales, Sydney, Australia.; Faculty of Health, University of Newcastle, Newcastle NSW, Australia; Hunter Area Pathology Service, John Hunter Hospital, Newcastle, New South Wales, Australia.; Centre for Healthy Brain Ageing, School of Psychiatry, UNSW Medicine, University of New South Wales, Sydney, Australia; Neuropsychiatric Institute, Prince of Wales Hospital, Barker Street, Randwick, NSW, Australia.; Hunter Medical Research Institute, Newcastle, Australia; Hunter Area Pathology Service, John Hunter Hospital, Newcastle, New South Wales, Australia.; Centre for Healthy Brain Ageing, School of Psychiatry, UNSW Medicine, University of New South Wales, Sydney, Australia. Electronic address: [email protected].

DOI: 10.1016/j.mad.2018.06.002

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MeSH Terms: Age Factors, Aged, 80 and over, Female, Genotype, Healthy Aging, Heredity, Humans, Longevity, Male, Pedigree, Phenotype, Polymorphism, Genetic