Targeted sequencing of the 9p21.3 region reveals association with reduced disease risks in Ashkenazi Jewish centenarians

Yizhou Zhu; Seungjin Ryu; Archana Tare; Nir Barzilai; Gil Atzmon; Yousin Suh

doi:10.1111/acel.13962

Targeted sequencing of the 9p21.3 region reveals association with reduced disease risks in Ashkenazi Jewish centenarians

Yizhou Zhu, Seungjin Ryu, Archana Tare, Nir Barzilai, Gil Atzmon, Yousin Suh

Department of Human Biology

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

Abstract

Genome-wide association studies (GWAS) have pinpointed the chromosomal locus 9p21.3 as a genetic hotspot for various age-related disorders. Common genetic variants in this locus are linked to multiple traits, including coronary artery diseases, cancers, and diabetes. Centenarians are known for their reduced risk and delayed onset of these conditions. To investigate whether this evasion of disease risks involves diminished genetic risks in the 9p21.3 locus, we sequenced this region in an Ashkenazi Jewish centenarian cohort (centenarians: n = 450, healthy controls: n = 500). Risk alleles associated with cancers, glaucoma, CAD, and T2D showed a significant depletion in centenarians. Furthermore, the risk and non-risk genotypes are linked to two distinct low-frequency variant profiles, enriched in controls and centenarians, respectively. Our findings provide evidence that the extreme longevity cohort is associated with collectively lower risks of multiple age-related diseases in the 9p21.3 locus.

Original language	English
Journal	Aging Cell
Early online date	22 Aug 2023
DOIs	https://doi.org/10.1111/acel.13962
State	Published - Oct 2023

Bibliographical note

Funding Information:
Research in the Suh lab was supported by the National Institute of Health (AG017242, DK127778, AG076040, AG069750, AG061521, GM104459, AG056278, AG057341, AG057433, AG057706), a grant GCRLE‐1320 from the Global Consortium for Reproductive Longevity and Equality at the Buck Institute, made possible by the Bia‐Echo Foundation, and a grant from The Simons Foundation.

Publisher Copyright:
© 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.

Keywords

9p21
age-related disease
aging
centenarians
longevity
population genomics

ASJC Scopus subject areas

Aging
Cell Biology

UN SDGs

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

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10.1111/acel.13962

Cite this

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title = "Targeted sequencing of the 9p21.3 region reveals association with reduced disease risks in Ashkenazi Jewish centenarians",

abstract = "Genome-wide association studies (GWAS) have pinpointed the chromosomal locus 9p21.3 as a genetic hotspot for various age-related disorders. Common genetic variants in this locus are linked to multiple traits, including coronary artery diseases, cancers, and diabetes. Centenarians are known for their reduced risk and delayed onset of these conditions. To investigate whether this evasion of disease risks involves diminished genetic risks in the 9p21.3 locus, we sequenced this region in an Ashkenazi Jewish centenarian cohort (centenarians: n = 450, healthy controls: n = 500). Risk alleles associated with cancers, glaucoma, CAD, and T2D showed a significant depletion in centenarians. Furthermore, the risk and non-risk genotypes are linked to two distinct low-frequency variant profiles, enriched in controls and centenarians, respectively. Our findings provide evidence that the extreme longevity cohort is associated with collectively lower risks of multiple age-related diseases in the 9p21.3 locus.",

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note = "Funding Information: Research in the Suh lab was supported by the National Institute of Health (AG017242, DK127778, AG076040, AG069750, AG061521, GM104459, AG056278, AG057341, AG057433, AG057706), a grant GCRLE‐1320 from the Global Consortium for Reproductive Longevity and Equality at the Buck Institute, made possible by the Bia‐Echo Foundation, and a grant from The Simons Foundation. Publisher Copyright: {\textcopyright} 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.",

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AU - Atzmon, Gil

AU - Suh, Yousin

N1 - Funding Information: Research in the Suh lab was supported by the National Institute of Health (AG017242, DK127778, AG076040, AG069750, AG061521, GM104459, AG056278, AG057341, AG057433, AG057706), a grant GCRLE‐1320 from the Global Consortium for Reproductive Longevity and Equality at the Buck Institute, made possible by the Bia‐Echo Foundation, and a grant from The Simons Foundation. Publisher Copyright: © 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.

PY - 2023/10

Y1 - 2023/10

N2 - Genome-wide association studies (GWAS) have pinpointed the chromosomal locus 9p21.3 as a genetic hotspot for various age-related disorders. Common genetic variants in this locus are linked to multiple traits, including coronary artery diseases, cancers, and diabetes. Centenarians are known for their reduced risk and delayed onset of these conditions. To investigate whether this evasion of disease risks involves diminished genetic risks in the 9p21.3 locus, we sequenced this region in an Ashkenazi Jewish centenarian cohort (centenarians: n = 450, healthy controls: n = 500). Risk alleles associated with cancers, glaucoma, CAD, and T2D showed a significant depletion in centenarians. Furthermore, the risk and non-risk genotypes are linked to two distinct low-frequency variant profiles, enriched in controls and centenarians, respectively. Our findings provide evidence that the extreme longevity cohort is associated with collectively lower risks of multiple age-related diseases in the 9p21.3 locus.

AB - Genome-wide association studies (GWAS) have pinpointed the chromosomal locus 9p21.3 as a genetic hotspot for various age-related disorders. Common genetic variants in this locus are linked to multiple traits, including coronary artery diseases, cancers, and diabetes. Centenarians are known for their reduced risk and delayed onset of these conditions. To investigate whether this evasion of disease risks involves diminished genetic risks in the 9p21.3 locus, we sequenced this region in an Ashkenazi Jewish centenarian cohort (centenarians: n = 450, healthy controls: n = 500). Risk alleles associated with cancers, glaucoma, CAD, and T2D showed a significant depletion in centenarians. Furthermore, the risk and non-risk genotypes are linked to two distinct low-frequency variant profiles, enriched in controls and centenarians, respectively. Our findings provide evidence that the extreme longevity cohort is associated with collectively lower risks of multiple age-related diseases in the 9p21.3 locus.

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Targeted sequencing of the 9p21.3 region reveals association with reduced disease risks in Ashkenazi Jewish centenarians

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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