Institut for Biomedicin

Lars Bolund

Novel loci and pathways significantly associated with longevity

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

DOI

  • Yi Zeng
  • ,
  • Chao Nie
  • ,
  • Junxia Min
  • ,
  • Xiaomin Liu
  • ,
  • Mengmeng Li
  • ,
  • Huashuai Chen
  • ,
  • Hanshi Xu
  • ,
  • Mingbang Wang
  • ,
  • Ting Ni
  • ,
  • Yang Li
  • ,
  • Han Yan
  • ,
  • Jin-Pei Zhang
  • ,
  • Chun Song
  • ,
  • Li-Qing Chi
  • ,
  • Han-Ming Wang
  • ,
  • Jie Dong
  • ,
  • Gu-Yan Zheng
  • ,
  • Li Lin
  • ,
  • Feng Qian
  • ,
  • Yanwei Qi
  • ,
  • Xiao Liu
  • ,
  • Hongzhi Cao
  • ,
  • Yinghao Wang
  • ,
  • Lijuan Zhang
  • ,
  • Zhaochun Li
  • ,
  • Yufeng Zhou
  • ,
  • Yan Wang
  • ,
  • Jiehua Lu
  • ,
  • Jianxin Li
  • ,
  • Ming Qi
  • ,
  • Lars Bolund
  • Anatoliy Yashin
  • ,
  • Kenneth C Land
  • ,
  • Simon Gregory
  • ,
  • Ze Yang
  • ,
  • William Gottschalk
  • ,
  • Wei Tao
  • ,
  • Jian Wang
  • ,
  • Jun Wang
  • ,
  • Xun Xu
  • ,
  • Harold Bae
  • ,
  • Marianne Nygaard
  • ,
  • Lene Christiansen
  • ,
  • Kaare Christensen
  • ,
  • Claudio Franceschi
  • ,
  • Michael W Lutz
  • ,
  • Jun Gu
  • ,
  • Qihua Tan
  • ,
  • Thomas Perls
  • ,
  • Paola Sebastiani
  • ,
  • Joris Deelen
  • ,
  • Eline Slagboom
  • ,
  • Elizabeth Hauser
  • ,
  • Huji Xu
  • ,
  • Xiao-Li Tian
  • ,
  • Huanming Yang
  • ,
  • James W Vaupel

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.

OriginalsprogEngelsk
TidsskriftScientific Reports
Vol/bind6
Sider (fra-til)21243
ISSN2045-2322
DOI
StatusUdgivet - 2016

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