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. Schork; Thomas T. Perls; Paola Sebastiani

doi:10.3390/ijms24010116

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

Medicine

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

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, 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 language	English (US)
Article number	116
Journal	International Journal of Molecular Sciences
Volume	24
Issue number	1
DOIs	https://doi.org/10.3390/ijms24010116
State	Published - Jan 2023

Keywords

genetic variants
human longevity
protein signatures

ASJC Scopus subject areas

Catalysis
Molecular Biology
Spectroscopy
Computer Science Applications
Physical and Theoretical Chemistry
Organic Chemistry
Inorganic Chemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Bae, H., Gurinovich, A., Karagiannis, T. T., Song, Z., Leshchyk, A., Li, M., Andersen, S. L., 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., ... Sebastiani, P. (2023). A Genome-Wide Association Study of 2304 Extreme Longevity Cases Identifies Novel Longevity Variants. International Journal of Molecular Sciences, 24(1), Article 116. https://doi.org/10.3390/ijms24010116

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 2023, 'A Genome-Wide Association Study of 2304 Extreme Longevity Cases Identifies Novel Longevity Variants', International Journal of Molecular Sciences, vol. 24, no. 1, 116. https://doi.org/10.3390/ijms24010116

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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, 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{\textquoteright}s disease, and disease progressions.",

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AU - Bae, Harold

AU - Gurinovich, Anastasia

AU - Karagiannis, Tanya T.

AU - Song, Zeyuan

AU - Leshchyk, Anastasia

AU - Li, Mengze

AU - Andersen, Stacy L.

AU - Arbeev, Konstantin

AU - Yashin, Anatoliy

AU - Zmuda, Joseph

AU - An, Ping

AU - Feitosa, Mary

AU - Giuliani, Cristina

AU - Franceschi, Claudio

AU - Garagnani, Paolo

AU - Mengel-From, Jonas

AU - Atzmon, Gil

AU - Barzilai, Nir

AU - Puca, Annibale

AU - Schork, Nicholas J.

AU - Perls, Thomas T.

AU - Sebastiani, Paola

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N2 - 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.

AB - 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.

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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