Broer Linda, van Duijn Cornelia M
Department of Epidemiology, Erasmus University Medical Center, Dr. Molewaterplein 50, PO-Box 2040, 3000 CA, Rotterdam, Netherlands,
Adv Exp Med Biol. 2015;847:107-25. doi: 10.1007/978-1-4939-2404-2_5.
Longevity is an extremely complex phenotype that is determined by environment, life style and genetics. Genome wide association studies (GWAS) have been a powerful tool to identify the genetic origin of other complex outcome with a similar heritability. In this chapter we discuss the findings all GWAS of longevity conducted to date. Various cut-off to define longevity have been used varying from 85+, 90+ and 100+ years and the impact of these difference are addressed in this chapter. The only consistent association emerging from GWAS to data is the APOE gene that has been already identified as a candidate gene. Although (GWAS) have identified biologically plausible genes and pathways, no new loci for longevity have been conclusively proven. A reason for not finding any replicated associations for longevity could be the complexity of the phenotype, although heterogeneity also underlies many other traits for which GWAS has been successful. One may argue that rare variants explain the high heritability of longevity and the segregation of the trait in families. Yet, whole genome analyses of GWAS data still suggest that over 80 % of the heritability is explained by common variants. Although findings of GWAS to date have been disappointing, there is ample opportunity to improve the statistical power of studies to find common variants with small effects. In the near future, joining of the published studies and new ones emerging may bring to surface new loci.
长寿是一种极其复杂的表型，由环境、生活方式和基因决定。全基因组关联研究（GWAS）一直是识别具有相似遗传力的其他复杂结果的遗传起源的有力工具。在本章中，我们讨论了迄今为止进行的所有长寿GWAS的研究结果。定义长寿的各种临界值各不相同，从85岁以上、90岁以上到100岁以上，本章将探讨这些差异的影响。GWAS迄今唯一一致出现的关联是已被确定为候选基因的载脂蛋白E（APOE）基因。尽管GWAS已经确定了生物学上合理的基因和途径，但尚未最终证明有新的长寿基因座。未能找到任何与长寿相关的重复关联的一个原因可能是该表型的复杂性，尽管异质性也是GWAS取得成功的许多其他性状的基础。有人可能会认为，罕见变异解释了长寿的高遗传力以及该性状在家族中的分离。然而，对GWAS数据的全基因组分析仍然表明，超过80%的遗传力是由常见变异解释的。尽管迄今为止GWAS的研究结果令人失望，但仍有充分的机会提高研究的统计效力，以发现具有微小效应的常见变异。在不久的将来，已发表研究与新出现研究的合并可能会揭示新的基因座。
