Centre for Healthy Brain Ageing, School of Psychiatry, UNSW Medicine, University of New South Wales, Sydney, Australia.
Hunter Medical Research Institute, Newcastle, Australia.
Mech Ageing Dev. 2018 Oct;175:24-34. doi: 10.1016/j.mad.2018.06.002. Epub 2018 Jun 8.
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.
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meta-analyses were performed if there were data from at least three independent studies available, including two unpublished additional cohorts.
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).
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.
许多因素促成了非凡的长寿，其中遗传起着重要作用。然而，迄今为止，对非凡长寿的遗传研究尚无定论。本综述旨在通过进行荟萃分析来确定与非凡长寿相关的遗传变异。
对先前与非凡长寿（85 岁以上）相关的遗传多态性进行荟萃分析。如果有至少三个独立研究的数据可用，包括两个未发表的额外队列，则对每个变体进行荟萃分析。
ACE rs4340、APOE ε2/3/4、FOXO3A rs2802292、KLOTHO KL-VS 和 IL6 rs1800795 这五个多态性与非凡长寿显著相关，汇总效应大小（优势比）范围从 0.42（APOE ε4）到 1.45（FOXO3A 男性）。
总的来说，观察到的显著变异的适度效应大小表明，许多遗传影响较小的基因在非凡长寿中发挥作用，这与其他多基因特征的结果一致。我们的结果还表明，与心血管健康相关的基因可能与非凡长寿有关。未来的研究应检查性别和种族的作用，并仔细考虑研究设计，包括选择适当的对照。
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