4.7 Article

Copy number variation associates with mortality in long-lived individuals: a genome-wide assessment

期刊

AGING CELL
卷 15, 期 1, 页码 49-55

出版社

WILEY
DOI: 10.1111/acel.12407

关键词

aging; copy number variation; deletions; genetics; long-lived individuals; mortality

资金

  1. INTERREG 4 A programme Syddanmark-Schleswig-K.E.R.N
  2. EU
  3. European Union [259679]
  4. VELUX Foundation
  5. Danish Agency for Science Technology and Innovation [09-063256]
  6. US National Institute of Health [P01AG08761]
  7. Danish Agency for Science, Technology and Innovation/The Danish Council for Independent Research [11-107308]
  8. Danish Interdisciplinary Research Council
  9. CERA Foundation (Lyon)
  10. AXA Research Fund, Paris
  11. Health Foundation (Helsefonden), Copenhagen, Denmark
  12. Innovation-Oriented Research Program on Genomics [SenterNovem IGE05007]
  13. Centre for Medical Systems Biology
  14. Netherlands Consortium for Healthy Ageing [050-060-810]
  15. Biobank-Based Integrative Omics Studies (BIOS) Consortium - BBMRI-NL
  16. Dutch government [NWO 184.021.007]

向作者/读者索取更多资源

Copy number variants (CNVs) represent a significant source of genetic variation in the human genome and have been implicated in numerous diseases and complex traits. To date, only a few studies have investigated the role of CNVs in human lifespan. To investigate the impact of CNVs on prospective mortality at the extreme end of life, where the genetic component of lifespan appears most profound, we analyzed genomewide CNV data in 603 Danish nonagenarians and centenarians (mean age 96.9 years, range 90.0-102.5 years). Replication was performed in 500 long-lived individuals from the Leiden Longevity Study (mean age 93.2 years, range 88.9-103.4 years). First, we assessed the association between the CNV burden of each individual (the number of CNVs, the average CNV length, and the total CNV length) and mortality and found a significant increase in mortality per 10 kb increase in the average CNV length, both for all CNVs (hazard ratio (HR) = 1.024, P = 0.002) and for duplications (HR = 1.011, P = 0.005), as well as per 100 kb increase in the total length of deletions (HR = 1.009, P = 0.0005). Next, we assessed the relation between specific deletions and duplications and mortality. Although no genome-wide significant associations were discovered, we identified six deletions and one duplication that showed consistent association with mortality in both or either of the sexes across both study populations. These results indicate that the genome-wide CNV burden, specifically the average CNV length and the total CNV length, associates with higher mortality in long-lived individuals.

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