Title | A Genome-Wide Association Study of 2304 Extreme Longevity Cases Identifies Novel Longevity Variants. |
Publication Type | Journal Article |
Year of Publication | 2022 |
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 |
Journal | Int J Mol Sci |
Volume | 24 |
Issue | 1 |
Date Published | 12/2022 |
ISSN | 1422-0067 |
Keywords | Aged, 80 and over, Alleles, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Longevity, Polymorphism, Single Nucleotide, Proteomics |
Abstract | 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, = 7.13 × 10) 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. |
DOI | 10.3390/ijms24010116 |
Alternate Journal | Int J Mol Sci |
PubMed ID | 36613555 |
PubMed Central ID | PMC9820206 |
Grant List | R01AG061844 / AG / NIA NIH HHS / United States U19AG023122 / NH / NIH HHS / United States U19AG063893 / NH / NIH HHS / United States UH2AG064704 / AG / NIA NIH HHS / United States |