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.

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Citation

Published Version (Please cite this version)

10.1038/srep21243

Publication Info

Zeng, Yi, Chao Nie, Junxia Min, Xiaomin Liu, Mengmeng Li, Huashuai Chen, Hanshi Xu, Mingbang Wang, et al. (2016). Novel loci and pathways significantly associated with longevity. Sci Rep, 6. p. 21243. 10.1038/srep21243 Retrieved from https://hdl.handle.net/10161/14652.

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Scholars@Duke

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.

Yashin

Anatoli I. Yashin

Research Professor in the Social Science Research Institute
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 1986. I served as Chair of Sociology from January 1986 to August 1997. My main research interests are contemporary social trends and quality-of-life measurement, social problems, demography, criminology, organizations, and mathematical and statistical models and methods for the study of social and demographic processes. I have done extensive research in each of these areas and have been elected a Fellow of the American Statistical Association (1978), the Sociological Research Association (1981), the American Association for the Advancement of Science (1992), the International Society for Quality-of-Life Studies (1997), and the American Society of Criminology (2004). I teach Contemporary Social Problems (SOCIOL 111), Advanced Methods of Demographic Analysis, and the Demography of Aging Proseminar (SOCIOL 750S). My other interests include tennis, jogging (10 kilometers), and music.

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 diseases using genetic, genomic, and epigenetic approaches. Dr. Gregory’s primary areas of research involve understanding the molecular processes associated with disease development and progression in brain tumors and Alzheimer’s disease, novel drug induced white matter injury repair in multiple sclerosis, and social and behavioral response to oxytocin treatment animal models of autism. 

He is broadly regarded across Duke as a leader in the development of novel single cell and spatial molecular technologies towards understanding the pathogenic mechanisms of disease development. Dr. Gregory is also the Section Chair of Genomics and Epigenetics at the DMPI and Director of the Duke Center of Autoimmunity and MS in the Department of Neurology.

Gottschalk

William Kirby Gottschalk

Assistant Professor in Neurology
Lutz

Michael William Lutz

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.

Hauser

Elizabeth Rebecca Hauser

Professor of Biostatistics & Bioinformatics

The incorporation of personalized medicine to all areas of human health represents a turning point for human genetics studies, a point at which the discoveries made have real implications for clinical medicine.  It is important for students to gain experience in how human genetics studies are conducted and how results of those studies may be used.  As a statistical geneticist and biostatistician my research interests are focused on developing and applying statistical methods to search for genes causing common human diseases.  My research programs combine development and application of statistical methods for genetic studies, with a particular emphasis on understanding the joint effects of genes and environment. 

These studies I work on cover diverse areas in biomedicine but are always collaborative, with the goal of bringing robust data science and statistical methods to the project.  Collaborative studies include genetic and ‘omics studies of cardiovascular disease, health effects of air pollution, genetic analysis of adherence to an exercise program, genetic analysis in evaluating colon cancer risk, genetic analysis of suicide, and systems biology analysis of Gulf War Illness.

Keywords: human genetics, genetic association, gene mapping, genetic epidemiology, statistical genetics, biostatistics, cardiovascular disease, computational biology, diabetes, aging, colon cancer, colon polyps, kidney disease, Gulf War Illness, exercise behavior, suicide





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