Research Paper|Volume 10, Issue 6|pp 1206—1222

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

Xin Zhao^1,^13,¹⁴, Xiaomin Liu^1,¹⁵, Aiping Zhang¹, Huashuai Chen^2,^4,⁵, Qing Huo¹, Weiyang Li¹, Rui Ye¹, Zhihua Chen¹, Liping Liang¹, Qiong A. Liu¹, Juan Shen¹, Xin Jin¹, Wenwen Li³, Marianne Nygaard⁶, Xiao Liu¹, Yong Hou¹, Ting Ni⁷, Lars Bolund^1,⁸, William Gottschalk⁹, Wei Tao¹⁰, Jun Gu¹⁰, Xiao-Li Tian¹¹, Huanming Yang¹, Jian Wang¹, Xun Xu¹, Michael W. Lutz⁹, Junxia Min³, Yi Zeng^2,⁴, Chao Nie^1,¹³

¹BGI Shenzhen, Shenzhen 518083, China
²Center for the Study of Aging and Human Development and Geriatrics Division, Medical School of Duke University, Durham NC 27710, USA
³The First Affiliated Hospital, Institute of Translational Medicine, School of Medicine, Zhejiang University, Hangzhou 310058, China
⁴Center for Healthy Aging and Development Studies, Raissun Institute for Advanced Studies, National School of Development, Peking University, Beijing 10080, China
⁵Business School of Xiangtan University, Xiangtan 411105, China
⁶The Danish Aging Research Center, Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Odense C 5000, Denmark
⁷State Key Laboratory of Genetics Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai 200433, China
⁸Department of Biomedicine, Aarhus University, Aarhus 8000, Denmark
⁹Department of Neurology, Medical Center, Duke University, Durham, NC 27704, USA
¹⁰School of Life Sciences, Peking University, Beijing 100080, China
¹¹Department of Human Population Genetics, Human Aging Research Institute and School of Life Science Nanchang University, Nanchang 330000, China
¹²James D. Watson Institute of Genome Sciences, Hangzhou 310058, China
¹³BGI Education Center, University of Chinese Academy of Sciences, Shenzhen 518083, China
¹⁴College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
¹⁵School of Bioscience and Bioengineering, South China University of Technology, Guangzhou, China

* * Equal contribution

Received: January 13, 2018Accepted: May 30, 2018Published: June 5, 2018

https://doi.org/10.18632/aging.101461

Copyright: © 2018 Zhao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

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.