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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http://hdl.handle.net/10161/14652Published Version (Please cite this version)
10.1038/srep21243Publication Info
Bae, H; Bolund, L; Cao, H; Chen, H; Chi, L-Q; Christensen, Kaare; ... Zhou, Y (2016). Novel loci and pathways significantly associated with longevity. Sci Rep, 6. pp. 21243. 10.1038/srep21243. Retrieved from http://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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William Kirby Gottschalk
Assistant Professor of Neurology
Simon Gray Gregory
Professor in Neurology
My principal area of research involves elucidating the molecular mechanisms underlying
multi-factorial diseases. My lab is primarily interested identifying the complex genetic
factors that give rise to multiple sclerosis, autism and cardiovascular disease. We
are using targeted approaches to identify differential methylation of the oxytocin
receptor gene (OXTR) in individuals with autism, and applying these data to an NICHD
funded ACE award, SOARS-B, to assess long term use of oxytocin nasal spr
Elizabeth Rebecca Hauser
Professor of Biostatistics and 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 the research for genes for common diseases.
Kenneth C. Land
John Franklin Crowell 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
Jianfeng Lu
Associate Professor of Mathematics
Jianfeng Lu is an applied mathematician interested in mathematical analysis and algorithm
development for problems from computational physics, theoretical chemistry, materials
science and other related fields.More specifically, his current research focuses include:Electronic
structure and many body problems; quantum molecular dynamics; multiscale modeling
and analysis; rare events and sampling techniques.
Michael William Lutz
Assistant Professor of 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 in the Sanford School of Public Policy
Anatoli I. Yashin
Research Professor in the Social Science Research Institute
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