Journal Article

Novel loci and pathways significantly associated with longevity

Tao, Wei, Perls, Thomas, Cao, Hongzhi, Gottschalk, William, Zhang, Lijuan, Qi, Ming, Liu, Xiao, Nygaard, Marianne, Song, Chun, Christiansen, Lene, Bolund, Lars, Sebastiani, Paola, Ni, Ting, Hauser, Elizabeth, Zeng, Yi, Deelen, Joris, Chen, Huashuai, Vaupel, James W., Yang, Huanming, Tian, Xiao-Li, Lu, Jiehua, Lin, Li, Christensen, Kaare, Li, Zhaochun, Dong, Jie, Qi, Yanwei, Tan, Qihua, Chi, Li-Qing, Land, Kenneth C., Min, Junxia, Wang, Mingbang, Bae, Harold, Xu, Xun, Li, Mengmeng, Slagboom, Eline, Zhang, Jin-Pei, Yan, Han, Wang, Yan, Wang, Yinghao, Li, Jianxin, Nie, Chao, Wang, Han-Ming, Xu, Hanshi, Yashin, Anatoliy, Yang, Ze, Gu, Jun, Wang, Jian, Franceschi, Claudio, Lutz, Michael W., Xu, Huji, Liu, Xiaomin, Zhou, Yufeng, Wang, Jun, Qian, Feng, Li, Yang, Zheng, Gu-Yan, Gregory, Simon

2016

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/208/721 / 692/53/2423 / 692/700/1518 / Aging / Apolipoprotein E / Apolipoproteins E - genetics / Asian Continental Ancestry Group - genetics / Calcium / Calcium signalling / Centenarians / China / Environmental stress / Gene Regulatory Networks / Genetic Loci / Genetic variance / Genome-wide association studies / Genome-Wide Association Study / Genomes / Geriatrics / Humanities and Social Sciences / Humans / Immune response / Interleukin 6 / Longevity / Longevity - genetics / MAP kinase / Membrane Transport Proteins - genetics / Metabolism / multidisciplinary / Oldest old people / Polymorphism, Single Nucleotide / Principal Component Analysis / Science / Science (multidisciplinary) / Signal transduction / Single-nucleotide polymorphism / Starch / Sucrose