Novel loci and pathways significantly associated with longevity.

Bae, H; Bolund, L; Cao, H; Chen, H; Chi, L-Q; Christensen, Kaare; Christiansen, L; Deelen, J; Dong, Jie; Franceschi, Claudio; Gottschalk, William Kirby; Gregory, Simon Gray; Gu, J; Hauser, Elizabeth Rebecca; Land, Kenneth C; Li, J; Li, M; Li, Y; Li, Z; Lin, L; Liu, X; Liu, X; Lu, Jianfeng; Lutz, Michael William; Min, J; Ni, T; Nie, C; Nygaard, M; Perls, T; Qi, M; Qi, Y; Qian, F; Sebastiani, P; Slagboom, E; Song, C; Tan, Q; Tao, W; Tian, X-L; Vaupel, James Walton; Wang, H-M; Wang, J; Wang, J; Wang, M; Wang, Y; Wang, Y; Xu, H; Xu, H; Xu, X; Yan, H; Yang, Huanming; Yang, Z; Yashin, Anatoli I; Zeng, Y; Zhang, J-P; Zhang, L; Zheng, G-Y; Zhou, Y

doi:10.1038/srep21243

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.

Publication 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.

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Scholars@Duke

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.