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Four Genome-Wide Association Studies Identify New Extreme Longevity Variants.


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.

SUBMITTER: Sebastiani P 

PROVIDER: S-EPMC5861867 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Four Genome-Wide Association Studies Identify New Extreme Longevity Variants.

Sebastiani Paola P   Gurinovich Anastasia A   Bae Harold H   Andersen Stacy S   Malovini Alberto A   Atzmon Gil G   Villa Francesco F   Kraja Aldi T AT   Ben-Avraham Danny D   Barzilai Nir N   Puca Annibale A   Perls Thomas T TT  

The journals of gerontology. Series A, Biological sciences and medical sciences 20171001 11


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 differenti  ...[more]

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