Format

Send to

Choose Destination
Aging (Albany NY). 2018 Jun 5;10(6):1206-1222. doi: 10.18632/aging.101461.

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

Zhao X#1,2,3, Liu X#1,4, Zhang A#1, Chen H#5,6,7, Huo Q1, Li W1, Ye R1, Chen Z1, Liang L1, Liu QA1, Shen J1, Jin X1, Li W8, Nygaard M9, Liu X1, Hou Y1, Ni T10, Bolund L1,11, Gottschalk W12, Tao W13, Gu J13, Tian XL14, Yang H1, Wang J1, Xu X1, Lutz MW12, Min J8, Zeng Y5,6, Nie C1,2.

Author information

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

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.

KEYWORDS:

Han Chinese; copy number variation; genome association study; long-lived; longevity; middle-aged controls

Supplemental Content

Full text links

Icon for Impact Journals, LLC Icon for PubMed Central
Loading ...
Support Center