Gurinovich, Anastasia, Song, Zeyuan, Zhang, William, Federico, Anthony, Monti, Stefano, Anderson, Stacy L, Jennings, Lori, Barzilai, Nir, Millman, Sofiya, Perls, Thomas T and Sebastian, Paola (2021) Effect of longevity genetic variants on the molecular aging rate. GeroScience. ISSN 25092723

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.

Item Type:	Article
Keywords:	Extreme human longevity Genetic variants Molecular aging rate SOMAscan array
Date Deposited:	15 Jun 2021 00:45
Last Modified:	15 Jun 2021 00:45
URI:	https://oak.novartis.com/id/eprint/44208