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    Novel loci and pathways significantly associated with longevity.

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    Date
    2016-02-25
    Authors
    Bae, H
    Bolund, L
    Cao, H
    Chen, H
    Chi, L-Q
    Christensen, Kaare
    Christiansen, L
    Deelen, J
    Dong, Jie
    Franceschi, Claudio
    Gottschalk, William Kirby
    Gregory, Simon Gray
    Gu, J
    Hauser, Elizabeth Rebecca
    Land, Kenneth C
    Li, J
    Li, M
    Li, Y
    Li, Z
    Lin, L
    Liu, X
    Liu, X
    Lu, Jianfeng
    Lutz, Michael William
    Min, J
    Ni, T
    Nie, C
    Nygaard, M
    Perls, T
    Qi, M
    Qi, Y
    Qian, F
    Sebastiani, P
    Slagboom, E
    Song, C
    Tan, Q
    Tao, W
    Tian, X-L
    Vaupel, James Walton
    Wang, H-M
    Wang, J
    Wang, J
    Wang, M
    Wang, Y
    Wang, Y
    Xu, H
    Xu, H
    Xu, X
    Yan, H
    Yang, Huanming
    Yang, Z
    Yashin, Anatoli I
    Zeng, Y
    Zhang, J-P
    Zhang, L
    Zheng, G-Y
    Zhou, Y
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    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.
    Type
    Journal article
    Subject
    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
    Permalink
    http://hdl.handle.net/10161/14652
    Published Version (Please cite this version)
    10.1038/srep21243
    Publication Info
    Bae, H; Bolund, L; Cao, H; Chen, H; Chi, L-Q; Christensen, Kaare; ... Zhou, Y (2016). Novel loci and pathways significantly associated with longevity. Sci Rep, 6. pp. 21243. 10.1038/srep21243. Retrieved from http://hdl.handle.net/10161/14652.
    This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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    Scholars@Duke

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    Simon Gray Gregory

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    Elizabeth Rebecca Hauser

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    Kenneth C. Land

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    I received my Ph.D. in sociology and mathematics from the University of Texas at Austin in 1969. After a year of postdoctoral study in mathematical statistics at Columbia University in New York City, I taught there and was a member of the staff of the Russell Sage Foundation for three years. I then was successively a member of the faculties of the University of Illinois at Urbana Champaign and the University of Texas at Austin before joining the Duke Sociology Department as Chairman in
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    Jianfeng Lu

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    Jianfeng Lu is an applied mathematician interested in mathematical analysis and algorithm development for problems from computational physics, theoretical chemistry, materials science and other related fields.More specifically, his current research focuses include:Electronic structure and many body problems; quantum molecular dynamics; multiscale modeling and analysis; rare events and sampling techniques.
    Lutz

    Michael William Lutz

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    Vaupel

    James Walton Vaupel

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    Yashin

    Anatoli I. Yashin

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