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Novel loci and pathways significantly associated with longevity

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  • 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.
  • This is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by Nature Publishing Group. The published article can be found at: http://www.nature.com/articles/srep21243
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  • Zeng, Y., Nie, C., Min, J., Liu, X., Li, M., Chen, H., ... & Vaupel, J. W. (2016). Novel loci and pathways significantly associated with longevity. Scientific Reports, 6, 21243. doi:10.1038/srep21243
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  • 6
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  • This study is supported by the National Key Basic Research Program of China (2013CB530700) (XLT, TN, YZ), National Natural Science Foundation of China (71233001, 71490732) (YZ), NIA/NIH (R01 AG023627, YZ; Pepper Center Grant P30AG028716, ERH; U19AG023122, TP, PS). The EU GWAS on longevity was performed by the EU Longevity Genetics Consortium undertaken within the framework of European Union's Seventh Framework Programme (FP7/2007-2011) under grant agreement no 259679 (IDEAL).
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