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- Title
Effect of longevity genetic variants on the molecular aging rate.
- Authors
Gurinovich, Anastasia; Song, Zeyuan; Zhang, William; Federico, Anthony; Monti, Stefano; Andersen, Stacy L.; Jennings, Lori L.; Glass, David J.; Barzilai, Nir; Millman, Sofiya; Perls, Thomas T.; Sebastiani, Paola
- Abstract
We conducted a genome-wide association study of 1320 centenarians from the New England Centenarian Study (median age = 104 years) and 2899 unrelated controls using >9 M genetic variants imputed to the HRC panel of ~65,000 haplotypes. The genetic variants with the most significant associations were correlated to 4131 proteins that were profiled in the serum of a subset of 224 study participants using a SOMAscan array. The genetic associations were replicated in a genome-wide association study of 480 centenarians and ~800 controls of Ashkenazi Jewish descent. The proteomic associations were replicated in a proteomic scan of approximately 1000 Ashkenazi Jewish participants from a third cohort. The analysis replicated a protein signature associated with APOE genotypes and confirmed strong overexpression of BIRC2 (p < 5E−16) and under-expression of APOB in carriers of the APOE2 allele (p < 0.05). The analysis also discovered and replicated associations between longevity variants and slower changes of protein biomarkers of aging, including a novel protein signature of rs2184061 (CDKN2A/CDKN2B in chromosome 9) that suggests a genetic regulation of GDF15. The analyses showed that longevity variants correlate with proteome signatures that could be manipulated to discover healthy-aging targets.
- Subjects
AGING; GENOME-wide association studies; GENEALOGY; LONGEVITY; GENETIC regulation; CENTENARIANS
- Publication
GeroScience, 2021, Vol 43, Issue 3, p1237
- ISSN
2509-2715
- Publication type
Article
- DOI
10.1007/s11357-021-00376-4