Novel loci and pathways significantly associated with longevity

Yi Zeng; Chao Nie; Junxia Min; Xiaomin Liu; Mengmeng Li; Huashuai Chen; Hanshi Xu; Mingbang Wang; Ting Ni; Yang Li; Han Yan; Jin Pei Zhang; Chun Song; Li Qing Chi; Han Ming Wang; Jie Dong; Gu Yan Zheng; Li Lin; Feng Qian; Yanwei Qi; Xiao Liu; Hongzhi Cao; Yinghao Wang; Lijuan Zhang; Zhaochun Li; Yufeng Zhou; Yan Wang; Jiehua Lu; Jianxin Li; Ming Qi; Lars Bolund; Anatoliy Yashin; Kenneth C. Land; Simon Gregory; Ze Yang; William Gottschalk; Wei Tao; Jian Wang; Jun Wang; Xun Xu; Harold Bae; Marianne Nygaard; Lene Christiansen; Kaare Christensen; Claudio Franceschi; Michael W. Lutz; Jun Gu; Qihua Tan; Thomas Perls; Paola Sebastiani; Joris Deelen; Eline Slagboom; Elizabeth Hauser; Huji Xu; Xiao Li Tian; Huanming Yang; James W. Vaupel

doi:10.1038/srep21243

Novel loci and pathways significantly associated with longevity

Yi Zeng
, Chao Nie
, Junxia Min
, Xiaomin Liu
, Mengmeng Li
, Huashuai Chen
, Hanshi Xu
, Mingbang Wang
, Ting Ni
, Yang Li
, Han Yan
, Jin Pei Zhang
, Chun Song
, Li Qing Chi
, Han Ming Wang
, Jie Dong
, Gu Yan Zheng
, Li Lin
, Feng Qian
, Yanwei Qi

Xiao Liu, Hongzhi Cao, Yinghao Wang, Lijuan Zhang, Zhaochun Li, Yufeng Zhou, Yan Wang, Jiehua Lu, Jianxin Li, Ming Qi, Lars Bolund, Anatoliy Yashin, Kenneth C. Land, Simon Gregory, Ze Yang, William Gottschalk, Wei Tao, Jian Wang, Jun Wang, Xun Xu, Harold Bae, Marianne Nygaard, Lene Christiansen, Kaare Christensen, Claudio Franceschi, Michael W. Lutz, Jun Gu, Qihua Tan, Thomas Perls, Paola Sebastiani, Joris Deelen, Eline Slagboom, Elizabeth Hauser, Huji Xu, Xiao Li Tian, Huanming Yang, James W. Vaupel

Duke University
Peking University
BGI-Shenzhen
Zhejiang University
Navy Medical University
XiangTan University
Fudan University
Anhui Medical University
Aarhus University
Ministry of Health of People's Republic of China
University of Copenhagen
Oregon State University
University of Southern Denmark
University of Bologna
Boston University
Leiden University
Max Planck Institute for Demographic Research

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

164 Scopus citations

Abstract

Only two genome-wide significant loci associated with longevity have been identified so far, probably because of insufficient sample sizes of centenarians, whose genomes may harbor genetic variants associated with health and longevity. Here we report a genome-wide association study (GWAS) of Han Chinese with a sample size 2.7 times the largest previously published GWAS on centenarians. We identified 11 independent loci associated with longevity replicated in Southern-Northern regions of China, including two novel loci (rs2069837-IL6; rs2440012-ANKRD20A9P) with genome-wide significance and the rest with suggestive significance (P < 3.65 × 10^-5). Eight independent SNPs overlapped across Han Chinese, European and U.S. populations, and APOE and 5q33.3 were replicated as longevity loci. Integrated analysis indicates four pathways (starch, sucrose and xenobiotic metabolism; immune response and inflammation; MAPK; calcium signaling) highly associated with longevity (P ≤ 0.006) in Han Chinese. The association with longevity of three of these four pathways (MAPK; immunity; calcium signaling) is supported by findings in other human cohorts. Our novel finding on the association of starch, sucrose and xenobiotic metabolism pathway with longevity is consistent with the previous results from Drosophilia. This study suggests protective mechanisms including immunity and nutrient metabolism and their interactions with environmental stress play key roles in human longevity.

Original language	English
Article number	21243
Journal	Scientific Reports
Volume	6
DOIs	https://doi.org/10.1038/srep21243
State	Published - 25 Feb 2016
Externally published	Yes

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10.1038/srep21243

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@article{9084b130c0734d129156c998690b8552,

title = "Novel loci and pathways significantly associated with longevity",

abstract = "Only two genome-wide significant loci associated with longevity have been identified so far, probably because of insufficient sample sizes of centenarians, whose genomes may harbor genetic variants associated with health and longevity. Here we report a genome-wide association study (GWAS) of Han Chinese with a sample size 2.7 times the largest previously published GWAS on centenarians. We identified 11 independent loci associated with longevity replicated in Southern-Northern regions of China, including two novel loci (rs2069837-IL6; rs2440012-ANKRD20A9P) with genome-wide significance and the rest with suggestive significance (P < 3.65 × 10-5). Eight independent SNPs overlapped across Han Chinese, European and U.S. populations, and APOE and 5q33.3 were replicated as longevity loci. Integrated analysis indicates four pathways (starch, sucrose and xenobiotic metabolism; immune response and inflammation; MAPK; calcium signaling) highly associated with longevity (P ≤ 0.006) in Han Chinese. The association with longevity of three of these four pathways (MAPK; immunity; calcium signaling) is supported by findings in other human cohorts. Our novel finding on the association of starch, sucrose and xenobiotic metabolism pathway with longevity is consistent with the previous results from Drosophilia. This study suggests protective mechanisms including immunity and nutrient metabolism and their interactions with environmental stress play key roles in human longevity.",

author = "Yi Zeng and Chao Nie and Junxia Min and Xiaomin Liu and Mengmeng Li and Huashuai Chen and Hanshi Xu and Mingbang Wang and Ting Ni and Yang Li and Han Yan and Zhang, \{Jin Pei\} and Chun Song and Chi, \{Li Qing\} and Wang, \{Han Ming\} and Jie Dong and Zheng, \{Gu Yan\} and Li Lin and Feng Qian and Yanwei Qi and Xiao Liu and Hongzhi Cao and Yinghao Wang and Lijuan Zhang and Zhaochun Li and Yufeng Zhou and Yan Wang and Jiehua Lu and Jianxin Li and Ming Qi and Lars Bolund and Anatoliy Yashin and Land, \{Kenneth C.\} and Simon Gregory and Ze Yang and William Gottschalk and Wei Tao and Jian Wang and Jun Wang and Xun Xu and Harold Bae and Marianne Nygaard and Lene Christiansen and Kaare Christensen and Claudio Franceschi and Lutz, \{Michael W.\} and Jun Gu and Qihua Tan and Thomas Perls and Paola Sebastiani and Joris Deelen and Eline Slagboom and Elizabeth Hauser and Huji Xu and Tian, \{Xiao Li\} and Huanming Yang and Vaupel, \{James W.\}",

year = "2016",

month = feb,

day = "25",

doi = "10.1038/srep21243",

language = "英语",

volume = "6",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Research",

}

Zeng, Y, Nie, C, Min, J, Liu, X, Li, M, Chen, H, Xu, H, Wang, M, Ni, T, Li, Y, Yan, H, Zhang, JP, Song, C, Chi, LQ, Wang, HM, Dong, J, Zheng, GY, Lin, L, Qian, F, Qi, Y, Liu, X, Cao, H, Wang, Y, Zhang, L, Li, Z, Zhou, Y, Wang, Y, Lu, J, Li, J, Qi, M, Bolund, L, Yashin, A, Land, KC, Gregory, S, Yang, Z, Gottschalk, W, Tao, W, Wang, J, Wang, J, Xu, X, Bae, H, Nygaard, M, Christiansen, L, Christensen, K, Franceschi, C, Lutz, MW, Gu, J, Tan, Q, Perls, T, Sebastiani, P, Deelen, J, Slagboom, E, Hauser, E, Xu, H, Tian, XL, Yang, H & Vaupel, JW 2016, 'Novel loci and pathways significantly associated with longevity', Scientific Reports, vol. 6, 21243. https://doi.org/10.1038/srep21243

TY - JOUR

T1 - Novel loci and pathways significantly associated with longevity

AU - Zeng, Yi

AU - Nie, Chao

AU - Min, Junxia

AU - Liu, Xiaomin

AU - Li, Mengmeng

AU - Chen, Huashuai

AU - Xu, Hanshi

AU - Wang, Mingbang

AU - Ni, Ting

AU - Li, Yang

AU - Yan, Han

AU - Zhang, Jin Pei

AU - Song, Chun

AU - Chi, Li Qing

AU - Wang, Han Ming

AU - Dong, Jie

AU - Zheng, Gu Yan

AU - Lin, Li

AU - Qian, Feng

AU - Qi, Yanwei

AU - Liu, Xiao

AU - Cao, Hongzhi

AU - Wang, Yinghao

AU - Zhang, Lijuan

AU - Li, Zhaochun

AU - Zhou, Yufeng

AU - Wang, Yan

AU - Lu, Jiehua

AU - Li, Jianxin

AU - Qi, Ming

AU - Bolund, Lars

AU - Yashin, Anatoliy

AU - Land, Kenneth C.

AU - Gregory, Simon

AU - Yang, Ze

AU - Gottschalk, William

AU - Tao, Wei

AU - Wang, Jian

AU - Wang, Jun

AU - Xu, Xun

AU - Bae, Harold

AU - Nygaard, Marianne

AU - Christiansen, Lene

AU - Christensen, Kaare

AU - Franceschi, Claudio

AU - Lutz, Michael W.

AU - Gu, Jun

AU - Tan, Qihua

AU - Perls, Thomas

AU - Sebastiani, Paola

AU - Deelen, Joris

AU - Slagboom, Eline

AU - Hauser, Elizabeth

AU - Xu, Huji

AU - Tian, Xiao Li

AU - Yang, Huanming

AU - Vaupel, James W.

PY - 2016/2/25

Y1 - 2016/2/25

N2 - Only two genome-wide significant loci associated with longevity have been identified so far, probably because of insufficient sample sizes of centenarians, whose genomes may harbor genetic variants associated with health and longevity. Here we report a genome-wide association study (GWAS) of Han Chinese with a sample size 2.7 times the largest previously published GWAS on centenarians. We identified 11 independent loci associated with longevity replicated in Southern-Northern regions of China, including two novel loci (rs2069837-IL6; rs2440012-ANKRD20A9P) with genome-wide significance and the rest with suggestive significance (P < 3.65 × 10-5). Eight independent SNPs overlapped across Han Chinese, European and U.S. populations, and APOE and 5q33.3 were replicated as longevity loci. Integrated analysis indicates four pathways (starch, sucrose and xenobiotic metabolism; immune response and inflammation; MAPK; calcium signaling) highly associated with longevity (P ≤ 0.006) in Han Chinese. The association with longevity of three of these four pathways (MAPK; immunity; calcium signaling) is supported by findings in other human cohorts. Our novel finding on the association of starch, sucrose and xenobiotic metabolism pathway with longevity is consistent with the previous results from Drosophilia. This study suggests protective mechanisms including immunity and nutrient metabolism and their interactions with environmental stress play key roles in human longevity.

AB - Only two genome-wide significant loci associated with longevity have been identified so far, probably because of insufficient sample sizes of centenarians, whose genomes may harbor genetic variants associated with health and longevity. Here we report a genome-wide association study (GWAS) of Han Chinese with a sample size 2.7 times the largest previously published GWAS on centenarians. We identified 11 independent loci associated with longevity replicated in Southern-Northern regions of China, including two novel loci (rs2069837-IL6; rs2440012-ANKRD20A9P) with genome-wide significance and the rest with suggestive significance (P < 3.65 × 10-5). Eight independent SNPs overlapped across Han Chinese, European and U.S. populations, and APOE and 5q33.3 were replicated as longevity loci. Integrated analysis indicates four pathways (starch, sucrose and xenobiotic metabolism; immune response and inflammation; MAPK; calcium signaling) highly associated with longevity (P ≤ 0.006) in Han Chinese. The association with longevity of three of these four pathways (MAPK; immunity; calcium signaling) is supported by findings in other human cohorts. Our novel finding on the association of starch, sucrose and xenobiotic metabolism pathway with longevity is consistent with the previous results from Drosophilia. This study suggests protective mechanisms including immunity and nutrient metabolism and their interactions with environmental stress play key roles in human longevity.

UR - https://www.scopus.com/pages/publications/84959378751

U2 - 10.1038/srep21243

DO - 10.1038/srep21243

M3 - 文章

C2 - 26912274

AN - SCOPUS:84959378751

SN - 2045-2322

VL - 6

JO - Scientific Reports

JF - Scientific Reports

M1 - 21243

ER -

Novel loci and pathways significantly associated with longevity

Abstract

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