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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Bae, H; Gurinovich, A; Karagiannis, TT; Song, Z; Leshchyk, A; Li, M; Andersen, SL; Arbeev, K; Yashin, A; Zmuda, J; An, P; Feitosa, M; Giuliani, C; Franceschi, C; Garagnani, P; Mengel-From, J; Atzmon, G; Barzilai, N; Puca, A; Schork, NJ; Perls, TT; Sebastiani, P

Published Date

  • December 2022

Published In

Volume / Issue

  • 24 / 1

Start / End Page

  • 116 -

PubMed ID

  • 36613555

Pubmed Central ID

  • PMC9820206

Electronic International Standard Serial Number (EISSN)

  • 1422-0067

International Standard Serial Number (ISSN)

  • 1422-0067

Digital Object Identifier (DOI)

  • 10.3390/ijms24010116


  • eng