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

M. Revelas; A. Thalamuthu; C. Oldmeadow; T-J Evans; N.J. Armstrong; J.B. Kwok; H. Brodaty; P.R. Schofield; R.J. Scott; P.S. Sachdev; J.R. Attia; K.A. Mather

doi:10.1016/j.mad.2018.06.002

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

Journal article

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Peer reviewed

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

M. Revelas, A. Thalamuthu, C. Oldmeadow, T-J Evans, N.J. Armstrong, J.B. Kwok, H. Brodaty, P.R. Schofield, R.J. Scott, P.S. Sachdev, …

Mechanisms of Ageing and Development, Vol.175, pp.24-34

2018

DOI: https://doi.org/10.1016/j.mad.2018.06.002

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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meta-analyses were performed if there were data from at least three independent studies available, including two unpublished additional cohorts.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.

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Title: Review and meta-analysis of genetic polymorphisms associated with exceptional human longevity
Authors/Creators: M. Revelas (Author/Creator) - UNSW Sydney
A. Thalamuthu (Author/Creator) - UNSW Sydney
C. Oldmeadow (Author/Creator) - Hunter Medical Research Institute
T-J Evans (Author/Creator) - Hunter Medical Research Institute
N.J. Armstrong (Author/Creator) - UNSW Sydney
J.B. Kwok (Author/Creator) - Neuroscience Research Australia
H. Brodaty (Author/Creator) - UNSW Sydney
P.R. Schofield (Author/Creator) - Neuroscience Research Australia
R.J. Scott (Author/Creator) - John Hunter Hospital
P.S. Sachdev (Author/Creator) - UNSW Sydney
J.R. Attia (Author/Creator) - John Hunter Hospital
K.A. Mather (Author/Creator) - UNSW Sydney
Publication Details: Mechanisms of Ageing and Development, Vol.175, pp.24-34
Publisher: Elsevier
Identifiers: 991005541973007891
Copyright: © 2018 Elsevier B.V.
Murdoch Affiliation: School of Engineering and Information Technology
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration
Citation topics: 1 Clinical & Life Sciences; 1.264 Longevity; 1.264.618 Aging Mechanisms
Web Of Science research areas: Cell Biology; Geriatrics & Gerontology
ESI research areas: Molecular Biology & Genetics