Novel loci and pathways significantly associated with longevity.
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 articleSubject
Apolipoproteins EAsian Continental Ancestry Group
China
Gene Regulatory Networks
Genetic Loci
Genome-Wide Association Study
Humans
Longevity
Membrane Transport Proteins
Polymorphism, Single Nucleotide
Principal Component Analysis
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https://hdl.handle.net/10161/14652Published Version (Please cite this version)
10.1038/srep21243Publication 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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Show full item recordScholars@Duke
William Kirby Gottschalk
Assistant Professor in Neurology
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
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
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
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.
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.
Anatoli I. Yashin
Research Professor in the Social Science Research Institute
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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