Four Genome-Wide Association Studies Identify New Extreme Longevity Variants

Paola Sebastiani, Anastasia Gurinovich, Harold Bae, Stacy Andersen, Alberto Malovini, Gil Atzmon, Francesco Villa, Aldi T. Kraja, Danny Ben-Avraham, Nir Barzilai, Annibale Puca, Thomas T. Perls

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

The search for the genetic determinants of extreme human longevity has been challenged by the phenotype's rarity and its nonspecific definition by investigators. To address these issues, we established a consortium of four studies of extreme longevity that contributed 2,070 individuals who survived to the oldest one percentile of survival for the 1900 U.S. birth year cohort. We conducted various analyses to discover longevity-associated variants (LAV) and characterized those LAVs that differentiate survival to extreme age at death (eSAVs) from those LAVs that become more frequent in centenarians because of mortality selection (eg, survival to younger years). The analyses identified new rare variants in chromosomes 4 and 7 associated with extreme survival and with reduced risk for cardiovascular disease and Alzheimer's disease. The results confirm the importance of studying truly rare survival to discover those combinations of common and rare variants associated with extreme longevity and longer health span.

Original languageEnglish (US)
Pages (from-to)1453-1464
Number of pages12
JournalThe journals of gerontology. Series A, Biological sciences and medical sciences
Volume72
Issue number11
DOIs
StatePublished - Oct 12 2017

Fingerprint

Genome-Wide Association Study
Survival
Chromosomes, Human, Pair 4
Chromosomes, Human, Pair 7
Alzheimer Disease
Cardiovascular Diseases
Research Personnel
Parturition
Phenotype
Mortality
Health

Keywords

  • Genetic profiles
  • Genetic variants
  • Healthy aging
  • Human longevity

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

Cite this

Sebastiani, P., Gurinovich, A., Bae, H., Andersen, S., Malovini, A., Atzmon, G., ... Perls, T. T. (2017). Four Genome-Wide Association Studies Identify New Extreme Longevity Variants. The journals of gerontology. Series A, Biological sciences and medical sciences, 72(11), 1453-1464. https://doi.org/10.1093/gerona/glx027

Four Genome-Wide Association Studies Identify New Extreme Longevity Variants. / Sebastiani, Paola; Gurinovich, Anastasia; Bae, Harold; Andersen, Stacy; Malovini, Alberto; Atzmon, Gil; Villa, Francesco; Kraja, Aldi T.; Ben-Avraham, Danny; Barzilai, Nir; Puca, Annibale; Perls, Thomas T.

In: The journals of gerontology. Series A, Biological sciences and medical sciences, Vol. 72, No. 11, 12.10.2017, p. 1453-1464.

Research output: Contribution to journalArticle

Sebastiani, P, Gurinovich, A, Bae, H, Andersen, S, Malovini, A, Atzmon, G, Villa, F, Kraja, AT, Ben-Avraham, D, Barzilai, N, Puca, A & Perls, TT 2017, 'Four Genome-Wide Association Studies Identify New Extreme Longevity Variants', The journals of gerontology. Series A, Biological sciences and medical sciences, vol. 72, no. 11, pp. 1453-1464. https://doi.org/10.1093/gerona/glx027
Sebastiani, Paola ; Gurinovich, Anastasia ; Bae, Harold ; Andersen, Stacy ; Malovini, Alberto ; Atzmon, Gil ; Villa, Francesco ; Kraja, Aldi T. ; Ben-Avraham, Danny ; Barzilai, Nir ; Puca, Annibale ; Perls, Thomas T. / Four Genome-Wide Association Studies Identify New Extreme Longevity Variants. In: The journals of gerontology. Series A, Biological sciences and medical sciences. 2017 ; Vol. 72, No. 11. pp. 1453-1464.
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