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Novel loci and pathways significantly associated with longevity.

dc.contributor.author Bae, H
dc.contributor.author Bolund, L
dc.contributor.author Cao, H
dc.contributor.author Chen, H
dc.contributor.author Chi, L-Q
dc.contributor.author Christensen, Kaare
dc.contributor.author Christiansen, L
dc.contributor.author Deelen, J
dc.contributor.author Dong, Jie
dc.contributor.author Franceschi, Claudio
dc.contributor.author Gottschalk, William Kirby
dc.contributor.author Gregory, Simon Gray
dc.contributor.author Gu, J
dc.contributor.author Hauser, Elizabeth Rebecca
dc.contributor.author Land, Kenneth C
dc.contributor.author Li, J
dc.contributor.author Li, M
dc.contributor.author Li, Y
dc.contributor.author Li, Z
dc.contributor.author Lin, L
dc.contributor.author Liu, X
dc.contributor.author Liu, X
dc.contributor.author Lu, Jianfeng
dc.contributor.author Lutz, Michael William
dc.contributor.author Min, J
dc.contributor.author Ni, T
dc.contributor.author Nie, C
dc.contributor.author Nygaard, M
dc.contributor.author Perls, T
dc.contributor.author Qi, M
dc.contributor.author Qi, Y
dc.contributor.author Qian, F
dc.contributor.author Sebastiani, P
dc.contributor.author Slagboom, E
dc.contributor.author Song, C
dc.contributor.author Tan, Q
dc.contributor.author Tao, W
dc.contributor.author Tian, X-L
dc.contributor.author Vaupel, James Walton
dc.contributor.author Wang, H-M
dc.contributor.author Wang, J
dc.contributor.author Wang, J
dc.contributor.author Wang, M
dc.contributor.author Wang, Y
dc.contributor.author Wang, Y
dc.contributor.author Xu, H
dc.contributor.author Xu, H
dc.contributor.author Xu, X
dc.contributor.author Yan, H
dc.contributor.author Yang, Huanming
dc.contributor.author Yang, Z
dc.contributor.author Yashin, Anatoli I
dc.contributor.author Zeng, Y
dc.contributor.author Zhang, J-P
dc.contributor.author Zhang, L
dc.contributor.author Zheng, G-Y
dc.contributor.author Zhou, Y
dc.coverage.spatial England
dc.date.accessioned 2017-06-01T17:59:59Z
dc.date.available 2017-06-01T17:59:59Z
dc.date.issued 2016-02-25
dc.identifier https://www.ncbi.nlm.nih.gov/pubmed/26912274
dc.identifier srep21243
dc.identifier.uri http://hdl.handle.net/10161/14652
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.language eng
dc.relation.ispartof Sci Rep
dc.relation.isversionof 10.1038/srep21243
dc.subject Apolipoproteins E
dc.subject Asian Continental Ancestry Group
dc.subject China
dc.subject Gene Regulatory Networks
dc.subject Genetic Loci
dc.subject Genome-Wide Association Study
dc.subject Humans
dc.subject Longevity
dc.subject Membrane Transport Proteins
dc.subject Polymorphism, Single Nucleotide
dc.subject Principal Component Analysis
dc.title Novel loci and pathways significantly associated with longevity.
dc.type Journal article
pubs.author-url https://www.ncbi.nlm.nih.gov/pubmed/26912274
pubs.begin-page 21243
pubs.organisational-group Center for Population Health & Aging
pubs.organisational-group Center for the Study of Aging and Human Development
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Population Research Center
pubs.organisational-group Duke Population Research Institute
pubs.organisational-group Institutes and Centers
pubs.organisational-group Medicine
pubs.organisational-group Medicine, Geriatrics
pubs.organisational-group Neurology
pubs.organisational-group Neurology, Behavioral Neurology
pubs.organisational-group Sanford School of Public Policy
pubs.organisational-group School of Medicine
pubs.publication-status Published online
pubs.volume 6
dc.identifier.eissn 2045-2322


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