Institut for Biomedicin

Lars Bolund

The correlation of copy number variations with longevity in a genome-wide association study of Han Chinese

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

  • Xin Zhao, BGI-Shenzhen, 518083 Shenzhen, China; China National GeneBank-Shenzhen, BGI-Shenzhen, 518083 Shenzhen, China., BGI Education Center, University of Chinese Academy of Sciences, Shenzhen 518083, China., College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
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  • Xiaomin Liu, School of Bioscience and Bioengineering, South China University of Technology, Guangzhou, China.
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  • Aiping Zhang, BGI-Shenzhen, 518083 Shenzhen, China; China National GeneBank-Shenzhen, BGI-Shenzhen, 518083 Shenzhen, China.
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  • Huashuai Chen, Business School of Xiangtan University, Xiangtan 411105, China.
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  • Qing Huo, BGI-Shenzhen, 518083 Shenzhen, China; China National GeneBank-Shenzhen, BGI-Shenzhen, 518083 Shenzhen, China.
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  • Weiyang Li, BGI-Shenzhen, 518083 Shenzhen, China; China National GeneBank-Shenzhen, BGI-Shenzhen, 518083 Shenzhen, China.
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  • Rui Ye, BGI-Shenzhen, 518083 Shenzhen, China; China National GeneBank-Shenzhen, BGI-Shenzhen, 518083 Shenzhen, China.
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  • Zhihua Chen, BGI-Shenzhen, 518083 Shenzhen, China; China National GeneBank-Shenzhen, BGI-Shenzhen, 518083 Shenzhen, China.
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  • Liping Liang, BGI-Shenzhen, 518083 Shenzhen, China; China National GeneBank-Shenzhen, BGI-Shenzhen, 518083 Shenzhen, China.
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  • Qiong A Liu, BGI-Shenzhen, 518083 Shenzhen, China; China National GeneBank-Shenzhen, BGI-Shenzhen, 518083 Shenzhen, China.
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  • Juan Shen, BGI-Shenzhen, 518083 Shenzhen, China; China National GeneBank-Shenzhen, BGI-Shenzhen, 518083 Shenzhen, China.
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  • Xin Jin, BGI-Shenzhen, 518083 Shenzhen, China; China National GeneBank-Shenzhen, BGI-Shenzhen, 518083 Shenzhen, China.
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  • Wenwen Li, The First Affiliated Hospital, Institute of Translational Medicine, School of Medicine, Zhejiang University, Hangzhou 310058, China.
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  • Marianne Nygaard, The Danish Aging Research Center, Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Odense C 5000, Denmark.
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  • Xiao Liu, BGI-Shenzhen, 518083 Shenzhen, China; China National GeneBank-Shenzhen, BGI-Shenzhen, 518083 Shenzhen, China.
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  • Yong Hou, BGI-Shenzhen, 518083 Shenzhen, China; China National GeneBank-Shenzhen, BGI-Shenzhen, 518083 Shenzhen, China.
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  • Ting Ni, State Key Laboratory of Genetics Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai 200433, China.
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  • Lars Bolund
  • William Gottschalk, Department of Neurology, Medical Center, Duke University, Durham, NC 27704, USA.
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  • Wei Tao, School of Life Sciences, Peking University, Beijing 100080, China.
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  • Jun Gu, School of Life Sciences, Peking University, Beijing 100080, China.
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  • Xiao-Li Tian, Department of Human Population Genetics, Human Aging Research Institute and School of Life Science Nanchang University, Nanchang 330000, China.
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  • Huanming Yang, BGI-Shenzhen, 518083 Shenzhen, China; China National GeneBank-Shenzhen, BGI-Shenzhen, 518083 Shenzhen, China.
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  • Jian Wang, BGI-Shenzhen, 518083 Shenzhen, China; China National GeneBank-Shenzhen, BGI-Shenzhen, 518083 Shenzhen, China.
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  • Xun Xu, BGI-Shenzhen, 518083 Shenzhen, China; China National GeneBank-Shenzhen, BGI-Shenzhen, 518083 Shenzhen, China.
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  • Michael W Lutz, Department of Neurology, Medical Center, Duke University, Durham, NC 27704, USA.
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  • Junxia Min, The First Affiliated Hospital, Institute of Translational Medicine, School of Medicine, Zhejiang University, Hangzhou 310058, China.
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  • Yi Zeng, Center for Healthy Aging and Development Studies, Raissun Institute for Advanced Studies, National School of Development, Peking University, Beijing 10080, China.
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  • Chao Nie, BGI Education Center, University of Chinese Academy of Sciences, Shenzhen 518083, China.

Copy number variations (CNVs) have been shown to cause numerous diseases, however, their roles in human lifespan remain elusive. In this study, we investigate the association of CNVs with longevity by comparing the Han Chinese genomes of long-lived individuals from 90 to 117 years of age and the middle-aged from 30 to 65. Our data demonstrate that the numbers of CNVs, especially deletions, increase significantly in a direct correlation with longevity. We identify eleven CNVs that strongly associate with longevity; four of them locate in the chromosome bands, 7p11.2, 20q13.33, 19p12 and 8p23.3 and overlap partially with the CNVs identified in long-lived Danish or U.S. populations, while the other seven have not been reported previously. These CNV regions encode nineteen known genes, and some of which have been shown to affect aging-related phenotypes such as the shortening of telomere length (ZNF208), the risk of cancer (FOXA1, LAMA5, ZNF716), and vascular and immune-related diseases (ARHGEF10, TOR2A, SH2D3C). In addition, we found several pathways enriched in long-lived genomes, including FOXA1 and FOXA transcription factor networks involved in regulating aging or age-dependent diseases such as cancer. Thus, our study has identified longevity-associated CNV regions and their affected genes and pathways. Our results suggest that the human genome structures such as CNVs might play an important role in determining a long life in human.

OriginalsprogEngelsk
TidsskriftAging
Vol/bind10
Nummer6
Sider (fra-til)1206-1222
Antal sider17
ISSN1945-4589
DOI
StatusUdgivet - 5 jun. 2018

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