Max Planck Institute for Biology of Ageing, 50866, Cologne, Germany.
Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, 2300 RC, Leiden, The Netherlands.
Nat Commun. 2019 Aug 14;10(1):3669. doi: 10.1038/s41467-019-11558-2.
Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at death or at last contact was at or below the age corresponding to the 60th survival percentile. Consistent with previous reports, rs429358 (apolipoprotein E (ApoE) ε4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE ε2) shows the opposite. Moreover, rs7676745, located near GPR78, associates with lower odds of surviving to the 90th percentile age. Gene-level association analysis reveals a role for tissue-specific expression of multiple genes in longevity. Finally, genetic correlation of the longevity GWA results with that of several disease-related phenotypes points to a shared genetic architecture between health and longevity.
人类的长寿是可遗传的，但全基因组关联（GWA）研究的成功有限。在这里，我们对包括 11262/3484 例分别达到或超过第 90/99 个生存率百分位数的严格长寿表型定义的 GWA 研究进行了两项荟萃分析，以及 25483 例对照，其死亡或最后一次联系时的年龄达到或低于第 60 个生存率百分位数。与之前的报告一致，rs429358（载脂蛋白 E（ApoE）ε4）与达到第 90 和 99 个生存率百分位数的几率降低相关，而 rs7412（ApoE ε2）则相反。此外，位于 GPR78 附近的 rs7676745 与达到第 90 个生存率百分位数的几率降低相关。基因水平的关联分析揭示了多个基因在长寿中的组织特异性表达的作用。最后，长寿 GWA 结果与几个与疾病相关的表型的遗传相关性表明，健康和长寿之间存在共同的遗传结构。
