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Novel loci and pathways significantly associated with longevity.

Publication ,  Journal Article
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 ...
Published in: Sci Rep
February 25, 2016

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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Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

February 25, 2016

Volume

6

Start / End Page

21243

Location

England

Related Subject Headings

  • Principal Component Analysis
  • Polymorphism, Single Nucleotide
  • Mitochondrial Precursor Protein Import Complex Proteins
  • Membrane Transport Proteins
  • Longevity
  • Humans
  • Genome-Wide Association Study
  • Genetic Loci
  • Gene Regulatory Networks
  • China
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Zeng, Y., Nie, C., Min, J., Liu, X., Li, M., Chen, H., … Vaupel, J. W. (2016). Novel loci and pathways significantly associated with longevity. Sci Rep, 6, 21243. https://doi.org/10.1038/srep21243
Zeng, Yi, Chao Nie, Junxia Min, Xiaomin Liu, Mengmeng Li, Huashuai Chen, Hanshi Xu, et al. “Novel loci and pathways significantly associated with longevity.Sci Rep 6 (February 25, 2016): 21243. https://doi.org/10.1038/srep21243.
Zeng Y, Nie C, Min J, Liu X, Li M, Chen H, et al. Novel loci and pathways significantly associated with longevity. Sci Rep. 2016 Feb 25;6:21243.
Zeng, Yi, et al. “Novel loci and pathways significantly associated with longevity.Sci Rep, vol. 6, Feb. 2016, p. 21243. Pubmed, doi:10.1038/srep21243.
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, Cao H, Wang Y, Zhang L, Li Z, Zhou Y, Lu J, Li J, Qi M, Bolund L, Yashin A, Land KC, Gregory S, Yang Z, Gottschalk W, Tao W, 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, Tian X-L, Yang H, Vaupel JW. Novel loci and pathways significantly associated with longevity. Sci Rep. 2016 Feb 25;6:21243.

Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

February 25, 2016

Volume

6

Start / End Page

21243

Location

England

Related Subject Headings

  • Principal Component Analysis
  • Polymorphism, Single Nucleotide
  • Mitochondrial Precursor Protein Import Complex Proteins
  • Membrane Transport Proteins
  • Longevity
  • Humans
  • Genome-Wide Association Study
  • Genetic Loci
  • Gene Regulatory Networks
  • China