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

Department of Human Biology

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

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
Article number	116
Journal	International Journal of Molecular Sciences
Volume	24
Issue number	1
DOIs	https://doi.org/10.3390/ijms24010116
State	Published - 21 Dec 2022

Bibliographical note

Publisher Copyright:
© 2022 by the authors.

Keywords

Aged, 80 and over
Alleles
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Longevity/genetics
Polymorphism, Single Nucleotide
Proteomics

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10.3390/ijms24010116

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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. (2022). 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

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title = "A Genome-Wide Association Study of 2304 Extreme Longevity Cases Identifies Novel Longevity Variants",

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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month = dec,

day = "21",

doi = "10.3390/ijms24010116",

language = "English",

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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 2022, '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

TY - JOUR

T1 - A Genome-Wide Association Study of 2304 Extreme Longevity Cases Identifies Novel Longevity Variants

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

PY - 2022/12/21

Y1 - 2022/12/21

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.

KW - Aged, 80 and over

KW - Alleles

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Humans

KW - Longevity/genetics

KW - Polymorphism, Single Nucleotide

KW - Proteomics

UR - http://www.scopus.com/inward/record.url?scp=85145949320&partnerID=8YFLogxK

U2 - 10.3390/ijms24010116

DO - 10.3390/ijms24010116

M3 - Article

C2 - 36613555

AN - SCOPUS:85145949320

SN - 1661-6596

VL - 24

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

IS - 1

M1 - 116

ER -

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

Abstract

Bibliographical note

Keywords

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