Novel loci and pathways significantly associated with longevity Public Deposited

http://ir.library.oregonstate.edu/concern/articles/ht24wm45g

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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  • 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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  • 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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  • description.provenance : Approved for entry into archive by Patricia Black(patricia.black@oregonstate.edu) on 2016-04-05T16:24:50Z (GMT) No. of bitstreams: 3 krauserp900261.zip: 1695019 bytes, checksum: cfc9a566f65514adc142a3cfd2c4d260 (MD5) ZengNovelLociPathways.pdf: 1172809 bytes, checksum: 00d7e0bdfa518c3f7261ff6378c46f91 (MD5) ZengNovelLociPathwaysSupplementaryMaterial.pdf: 962343 bytes, checksum: a1cec24158ccd0a7ea907251e286396f (MD5)
  • description.provenance : Submitted by Open Access (openaccess@library.oregonstate.edu) on 2016-04-05T16:17:22Z No. of bitstreams: 2 ZengNovelLociPathways.pdf: 1172809 bytes, checksum: 00d7e0bdfa518c3f7261ff6378c46f91 (MD5) ZengNovelLociPathwaysSupplementaryMaterial.pdf: 962343 bytes, checksum: a1cec24158ccd0a7ea907251e286396f (MD5)
  • description.provenance : Made available in DSpace on 2016-04-05T16:24:50Z (GMT). No. of bitstreams: 3 krauserp900261.zip: 1695019 bytes, checksum: cfc9a566f65514adc142a3cfd2c4d260 (MD5) ZengNovelLociPathways.pdf: 1172809 bytes, checksum: 00d7e0bdfa518c3f7261ff6378c46f91 (MD5) ZengNovelLociPathwaysSupplementaryMaterial.pdf: 962343 bytes, checksum: a1cec24158ccd0a7ea907251e286396f (MD5) Previous issue date: 2016-02-25

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