A Genome-Wide Association Study of 2304 Extreme Longevity Cases Identifies Novel Longevity Variants

Harold Bae, Anastasia Gurinovich, Tanya T. Karagiannis, Zeyuan Song, Anastasia Leshchyk, Mengze Li, Stacy L. Andersen, Konstantin Arbeev, Anatoliy Yashin, Joseph Zmuda, Ping An, Mary Feitosa, Cristina Giuliani, Claudio Franceschi, Paolo Garagnani, Jonas Mengel-From, Gil Atzmon, Nir Barzilai, Annibale Puca, Nicholas J. SchorkThomas T. Perls, Paola Sebastiani

Research output: Contribution to journalArticlepeer-review


We performed a genome-wide association study (GWAS) of human extreme longevity (EL), defined as surviving past the 99th survival percentile, by aggregating data from four centenarian studies. The combined data included 2304 EL cases and 5879 controls. The analysis identified a locus in CDKN2B-AS1 (rs6475609, p = 7.13 × 10−8) that almost reached genome-wide significance and four additional loci that were suggestively significant. Among these, a novel rare variant (rs145265196) on chromosome 11 had much higher longevity allele frequencies in cases of Ashkenazi Jewish and Southern Italian ancestry compared to cases of other European ancestries. We also correlated EL-associated SNPs with serum proteins to link our findings to potential biological mechanisms that may be related to EL and are under genetic regulation. The findings from the proteomic analyses suggested that longevity-promoting alleles of significant genetic variants either provided EL cases with more youthful molecular profiles compared to controls or provided some form of protection from other illnesses, such as Alzheimer’s disease, and disease progressions.

Original languageAmerican English
Article number116
Issue number1
StatePublished - 21 Dec 2022


  • Aged, 80 and over
  • Alleles
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Longevity/genetics
  • Polymorphism, Single Nucleotide
  • Proteomics


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