Dataset Information

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.

SUBMITTER: Zeng Y

PROVIDER: S-EPMC4766491 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Novel loci and pathways significantly associated with longevity.

Zeng Yi Y Nie Chao C Min Junxia J Liu Xiaomin X Li Mengmeng M Chen Huashuai H Xu Hanshi H Wang Mingbang M Ni Ting T Li Yang Y Yan Han H Zhang Jin-Pei JP Song Chun C Chi Li-Qing LQ Wang Han-Ming HM Dong Jie J Zheng Gu-Yan GY Lin Li L Qian Feng F Qi Yanwei Y Liu Xiao X Cao Hongzhi H Wang Yinghao Y Zhang Lijuan L Li Zhaochun Z Zhou Yufeng Y Wang Yan Y Lu Jiehua J Li Jianxin J Qi Ming M Bolund Lars L Yashin Anatoliy A Land Kenneth C KC Gregory Simon S Yang Ze Z Gottschalk William W Tao Wei W Wang Jian J Wang Jun J Xu Xun X Bae Harold H Nygaard Marianne M Christiansen Lene L Christensen Kaare K Franceschi Claudio C Lutz Michael W MW Gu Jun J Tan Qihua Q Perls Thomas T Sebastiani Paola P Deelen Joris J Slagboom Eline E Hauser Elizabeth E Xu Huji H Tian Xiao-Li XL Yang Huanming H Vaupel James W JW

Scientific reports 20160225

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, i ...[more]

PMID: 26912274

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Project description:The aim of the present study was to extract potential sub‑pathway biomarkers for spondyloarthropathy (SpA)/ankylosing spondylitis (AS) using a sub‑pathway strategy. SpA/AS‑relevant data, reference pathways and long non‑coding (lnc)RNA‑micro (mi)RNA‑mRNA interactions were downloaded. The seed pathways based on Kyoto Encyclopedia of Genes and Genomes pathways and the mRNAs in the co‑expressed lncRNA‑mRNA interactions were extracted. Sub‑pathways regulated by lncRNA were selected after establishing condition‑specific lncRNA competitively regulated pathways (LCRP) network. Significant sub‑pathways were further identified using the attract method. These significant sub‑pathways were evaluated in the other independent published AS microarray data (E‑GEOD‑25101) using in silico validation. In addition, to uncover SpA/AS‑relevant lncRNAs, the degree analysis for all nodes in the LCRP network was conducted. A total of 35 lncRNAs, 131 mRNAs and 145 co‑expressed interactions were identified. When entering these 131 mRNAs into the reference pathways, 82 seed pathways were extracted, which were transformed into undirected graphs, and the 35 lncRNAs were mapped to the pathway graphs to further establish the condition‑specific LCRP network. Based on degree analysis, four hub lncRNAs were selected, including C14orf169, LINC00242, LINC00116 and LINC00482. It was identified that 35 lncRNAs competitively regulating sub‑pathways were involved in 56 complete pathways. Among these, the top three sub‑pathways were path: 04010_1, which was a subregion of the mitogen‑activated protein kinase (MAPK) signaling pathway; path: 04062‑1, an important subregion in the chemokine signaling pathway; and path: 04066_2, was a part of HIF‑1 signaling pathway. Furthermore, it was validated consistently in the separate microarray data set E‑GEOD‑25101. Cancer‑associated pathways and hub node C14orf169 were identified in validation. Sub‑pathways, including the MAPK signaling pathway and chemokine signaling pathway, and hub lncRNA (C14orf169) may serve important roles in SpA/AS.

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Novel loci and pathways significantly associated with longevity.

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Novel loci and pathways significantly associated with longevity.

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