ZengNovelLociPathways.pdf

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

Citeable URL: https://ir.library.oregonstate.edu/concern/articles/nc580p24r

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