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Novel loci and pathways significantly associated with longevity.

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Date
2016-02-25
Authors
Zeng, Yi
Nie, Chao
Min, Junxia
Liu, Xiaomin
Li, Mengmeng
Chen, Huashuai
Xu, Hanshi
Wang, Mingbang
Ni, Ting
Li, Yang
Yan, Han
Zhang, Jin-Pei
Song, Chun
Chi, Li-Qing
Wang, Han-Ming
Dong, Jie
Zheng, Gu-Yan
Lin, Li
Qian, Feng
Qi, Yanwei
Liu, Xiao
Cao, Hongzhi
Wang, Yinghao
Zhang, Lijuan
Li, Zhaochun
Zhou, Yufeng
Wang, Yan
Lu, Jiehua
Li, Jianxin
Qi, Ming
Bolund, Lars
Yashin, Anatoliy
Land, Kenneth C
Gregory, Simon
Yang, Ze
Gottschalk, William
Tao, Wei
Wang, Jian
Wang, Jun
Xu, Xun
Bae, Harold
Nygaard, Marianne
Christiansen, Lene
Christensen, Kaare
Franceschi, Claudio
Lutz, Michael W
Gu, Jun
Tan, Qihua
Perls, Thomas
Sebastiani, Paola
Deelen, Joris
Slagboom, Eline
Hauser, Elizabeth
Xu, Huji
Tian, Xiao-Li
Yang, Huanming
Vaupel, James W
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Abstract
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.
Type
Journal article
Subject
Apolipoproteins E
Asian Continental Ancestry Group
China
Gene Regulatory Networks
Genetic Loci
Genome-Wide Association Study
Humans
Longevity
Membrane Transport Proteins
Polymorphism, Single Nucleotide
Principal Component Analysis
Permalink
https://hdl.handle.net/10161/14652
Published Version (Please cite this version)
10.1038/srep21243
Publication Info
Zeng, Yi; Nie, Chao; Min, Junxia; Liu, Xiaomin; Li, Mengmeng; Chen, Huashuai; ... Vaupel, James W (2016). Novel loci and pathways significantly associated with longevity. Sci Rep, 6. pp. 21243. 10.1038/srep21243. Retrieved from https://hdl.handle.net/10161/14652.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Gottschalk

William Kirby Gottschalk

Assistant Professor in Neurology
Gregory

Simon Gray Gregory

Professor in Neurosurgery
Dr. Gregory is a tenured Professor and Director of the Brain Tumor Omics Program (BTOP) in the Duke Department of Neurosurgery, the Vice Chair of Research in the Department of Neurology, and Director of the Molecular Genomics Core at the Duke Molecular Physiology Institute.  As a neurogenomicist, Dr. Gregory applies the experience gained from leading the sequencing of chromosome 1 for the Human Genome Project to elucidating the mechanisms underlying multi-factorial
Hauser

Elizabeth Rebecca Hauser

Professor of Biostatistics & Bioinformatics
My research interests are focused on developing and applying statistical methods to search for genes causing common human diseases. Recent work has been in the development of statistical methods for genetic studies and in identifying optimal study designs for genetic studies of complex traits. As application of these methods to specific diseases has progressed it has become apparent that etiologic and genetic heterogeneity is a major stumbling block in identification of genes for common diseases
Land

Kenneth C. Land

John Franklin Crowell Distinguished Professor Emeritus of Sociology
I received my Ph.D. in sociology and mathematics from the University of Texas at Austin in 1969. After a year of postdoctoral study in mathematical statistics at Columbia University in New York City, I taught there and was a member of the staff of the Russell Sage Foundation for three years. I then was successively a member of the faculties of the University of Illinois at Urbana Champaign and the University of Texas at Austin before joining the Duke Sociology Department as Chairman in
Lutz

Michael William Lutz

Associate Professor in Neurology
Developing and using computational biology methods to understand the genetic basis of disease with a focus on Alzheimer’s Disease.   Recent work has focused on identification and validation of clinically-relevant biomarkers for Alzheimer’s disease and Alzheimer’s disease with Lewy bodies.
Vaupel

James Walton Vaupel

Research Professor Emeritus in the Sanford School of Public Policy
This author no longer has a Scholars@Duke profile, so the information shown here reflects their Duke status at the time this item was deposited.
Yashin

Anatoli I. Yashin

Research Professor in the Social Science Research Institute
Zeng

Yi Zeng

Professor in Medicine
(1) Socioeconomic, behavior, environmental and genetic determinants of healthy aging and healthy longevity; (2) Factors related to elderly disability and mental health; (3) Methods of family households and elderly living arrangements forecasting/analysis and their applications in health services and socioeconomic planning, and market studies; (4) Policy analysis in population aging, social welfare, retirement, and fertility transitions.
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