Novel loci and pathways significantly associated with longevity.

Zeng, Y; Nie, C; Min, J; Liu, X; Li, M; Chen, H; Xu, H; Wang, M; Ni, T; Li, Y; Yan, H; Zhang, J-P; Song, C; Chi, L-Q; Wang, H-M; Dong, J; Zheng, G-Y; 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, X-L; Yang, H; Vaupel, JW

Novel loci and pathways significantly associated with longevity.

Zeng, Y Nie, C Min, J Liu, X Li, M Chen, H Xu, H

Wang, M Ni, T Li, Y Yan, H Zhang, J-P Song, C Chi, L-Q Wang, H-M Dong, J Zheng, G-Y 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, X-L Yang, H Vaupel, JW

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Publisher:: Springer Nature
Publication Type:: Journal Article
Citation:: Sci Rep, 2016, 6, (1), pp. 21243
Issue Date:: 2016-02-25

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Field	Value	Language
dc.contributor.author	Zeng, Y
dc.contributor.author	Nie, C
dc.contributor.author	Min, J
dc.contributor.author	Liu, X
dc.contributor.author	Li, M
dc.contributor.author	Chen, H
dc.contributor.author	Xu, H https://orcid.org/0000-0003-1129-5337
dc.contributor.author	Wang, M
dc.contributor.author	Ni, T
dc.contributor.author	Li, Y
dc.contributor.author	Yan, H
dc.contributor.author	Zhang, J-P
dc.contributor.author	Song, C
dc.contributor.author	Chi, L-Q
dc.contributor.author	Wang, H-M
dc.contributor.author	Dong, J
dc.contributor.author	Zheng, G-Y
dc.contributor.author	Lin, L
dc.contributor.author	Qian, F
dc.contributor.author	Qi, Y
dc.contributor.author	Liu, X
dc.contributor.author	Cao, H
dc.contributor.author	Wang, Y
dc.contributor.author	Zhang, L
dc.contributor.author	Li, Z
dc.contributor.author	Zhou, Y
dc.contributor.author	Wang, Y
dc.contributor.author	Lu, J
dc.contributor.author	Li, J
dc.contributor.author	Qi, M
dc.contributor.author	Bolund, L
dc.contributor.author	Yashin, A
dc.contributor.author	Land, KC
dc.contributor.author	Gregory, S
dc.contributor.author	Yang, Z
dc.contributor.author	Gottschalk, W
dc.contributor.author	Tao, W
dc.contributor.author	Wang, J
dc.contributor.author	Wang, J
dc.contributor.author	Xu, X
dc.contributor.author	Bae, H
dc.contributor.author	Nygaard, M
dc.contributor.author	Christiansen, L
dc.contributor.author	Christensen, K
dc.contributor.author	Franceschi, C
dc.contributor.author	Lutz, MW
dc.contributor.author	Gu, J
dc.contributor.author	Tan, Q
dc.contributor.author	Perls, T
dc.contributor.author	Sebastiani, P
dc.contributor.author	Deelen, J
dc.contributor.author	Slagboom, E
dc.contributor.author	Hauser, E
dc.contributor.author	Xu, H https://orcid.org/0000-0003-1129-5337
dc.contributor.author	Tian, X-L
dc.contributor.author	Yang, H
dc.contributor.author	Vaupel, JW
dc.date.accessioned	2024-03-12T04:04:10Z
dc.date.available	2016-01-20
dc.date.available	2024-03-12T04:04:10Z
dc.date.issued	2016-02-25
dc.identifier.citation	Sci Rep, 2016, 6, (1), pp. 21243
dc.identifier.issn	2045-2322
dc.identifier.issn	2045-2322
dc.identifier.uri	http://hdl.handle.net/10453/176556
dc.description.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.
dc.format	Electronic
dc.language	eng
dc.publisher	Springer Nature
dc.relation.ispartof	Sci Rep
dc.relation.isbasedon	10.1038/srep21243
dc.rights	info:eu-repo/semantics/openAccess
dc.subject.mesh	Apolipoproteins E
dc.subject.mesh	Asian People
dc.subject.mesh	China
dc.subject.mesh	Gene Regulatory Networks
dc.subject.mesh	Genetic Loci
dc.subject.mesh	Genome-Wide Association Study
dc.subject.mesh	Humans
dc.subject.mesh	Longevity
dc.subject.mesh	Membrane Transport Proteins
dc.subject.mesh	Mitochondrial Precursor Protein Import Complex Proteins
dc.subject.mesh	Polymorphism, Single Nucleotide
dc.subject.mesh	Principal Component Analysis
dc.subject.mesh	Humans
dc.subject.mesh	Apolipoproteins E
dc.subject.mesh	Membrane Transport Proteins
dc.subject.mesh	Longevity
dc.subject.mesh	Polymorphism, Single Nucleotide
dc.subject.mesh	Principal Component Analysis
dc.subject.mesh	China
dc.subject.mesh	Gene Regulatory Networks
dc.subject.mesh	Genome-Wide Association Study
dc.subject.mesh	Genetic Loci
dc.subject.mesh	Mitochondrial Precursor Protein Import Complex Proteins
dc.subject.mesh	Asian People
dc.subject.mesh	Apolipoproteins E
dc.subject.mesh	Asian People
dc.subject.mesh	China
dc.subject.mesh	Gene Regulatory Networks
dc.subject.mesh	Genetic Loci
dc.subject.mesh	Genome-Wide Association Study
dc.subject.mesh	Humans
dc.subject.mesh	Longevity
dc.subject.mesh	Membrane Transport Proteins
dc.subject.mesh	Mitochondrial Precursor Protein Import Complex Proteins
dc.subject.mesh	Polymorphism, Single Nucleotide
dc.subject.mesh	Principal Component Analysis
dc.title	Novel loci and pathways significantly associated with longevity.
dc.type	Journal Article
utslib.citation.volume	6
utslib.location.activity	England
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	University of Technology Sydney/Faculty of Engineering and Information Technology/School of Computer Science
utslib.copyright.status	open_access	*
dc.date.updated	2024-03-12T04:04:06Z
pubs.issue	1
pubs.publication-status	Published online
pubs.volume	6
utslib.citation.issue	1

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.

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http://hdl.handle.net/10453/176556