Novel loci and pathways significantly associated with longevity.

Zeng, Yi

Nie, Chao

Min, Junxia

Liu, Xiaomin

Li, Mengmeng

Chen, Huashuai

Xu, Hanshi

Wang, Mingbang

Ni, Ting

Li, Yang

Yan, Han

Zhang, Jin-Pei

Song, Chun

Chi, Li-Qing

Wang, Han-Ming

Dong, Jie

Zheng, Gu-Yan

Lin, Li

Qian, Feng

Qi, Yanwei

Liu, Xiao

Cao, Hongzhi

Wang, Yinghao

Zhang, Lijuan

Li, Zhaochun

Zhou, Yufeng

Wang, Yan

Lu, Jiehua

Li, Jianxin

Qi, Ming

Bolund, Lars

Yashin, Anatoliy

Land, Kenneth C

Gregory, Simon

Yang, Ze

Gottschalk, William

Tao, Wei

Wang, Jian

Wang, Jun

Xu, Xun

Bae, Harold

Nygaard, Marianne

Christiansen, Lene

Christensen, Kaare

Franceschi, Claudio

Lutz, Michael W

Gu, Jun

Tan, Qihua

Perls, Thomas

Sebastiani, Paola

Deelen, Joris

Slagboom, Eline

Hauser, Elizabeth

Xu, Huji

Tian, Xiao-Li

Yang, Huanming

Vaupel, James W

England

2017-06-01T17:59:59Z

2017-06-01T17:59:59Z

2016-02-25

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.

https://www.ncbi.nlm.nih.gov/pubmed/26912274

srep21243

2045-2322

https://hdl.handle.net/10161/14652

eng

Springer Science and Business Media LLC

Sci Rep

10.1038/srep21243

Apolipoproteins E

Asian Continental Ancestry Group

China

Gene Regulatory Networks

Genetic Loci

Genome-Wide Association Study

Humans

Longevity

Membrane Transport Proteins

Polymorphism, Single Nucleotide

Principal Component Analysis

Novel loci and pathways significantly associated with longevity.

Journal article

Land, Kenneth C|0000-0002-9551-7314

Gregory, Simon|0000-0002-7805-1743

Gottschalk, William|0000-0001-6760-2338

Lutz, Michael W|0000-0001-8809-5574

Hauser, Elizabeth|0000-0003-0367-9189

https://www.ncbi.nlm.nih.gov/pubmed/26912274

21243

Center for Population Health & Aging

Center for the Study of Aging and Human Development

Clinical Science Departments

Duke

Duke Population Research Center

Duke Population Research Institute

Institutes and Centers

Medicine

Medicine, Geriatrics

Neurology

Neurology, Behavioral Neurology

Sanford School of Public Policy

School of Medicine

Published online

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