人类长寿的遗传学：来自长寿家族研究的新发现。
Genetics of Human Longevity From Incomplete Data: New Findings From the Long Life Family Study.
机构信息
Biodemography of Aging Research Unit, Social Science Research Institute, Duke University, Durham, North Carolina.
Thurston Arthritis Research Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
出版信息
J Gerontol A Biol Sci Med Sci. 2018 Oct 8;73(11):1472-1481. doi: 10.1093/gerona/gly057.
Abstract
The special design of the Long Life Family Study provides a unique opportunity to investigate the genetics of human longevity by analyzing data on exceptional lifespans in families. In this article, we performed two series of genome wide association studies of human longevity which differed with respect to whether missing lifespan data were predicted or not predicted. We showed that the use of predicted lifespan is most beneficial when the follow-up period is relatively short. In addition to detection of strong associations of SNPs in APOE, TOMM40, NECTIN2, and APOC1 genes with longevity, we also detected a strong new association with longevity of rs1927465, located between the CYP26A1 and MYOF genes on chromosome 10. The association was confirmed using data from the Health and Retirement Study. We discuss the biological relevance of the detected SNPs to human longevity.
摘要
长寿家族研究的特殊设计提供了一个独特的机会，通过分析家族中异常寿命的数据来研究人类长寿的遗传学。在本文中，我们进行了两项全基因组关联研究，这些研究在是否预测缺失寿命数据方面有所不同。我们表明，当随访期相对较短时，使用预测的寿命最有益。除了检测到 APOE、TOMM40、NECTIN2 和 APOC1 基因中的 SNP 与长寿的强烈关联外，我们还检测到与长寿的强烈新关联rs1927465，该 SNP 位于 10 号染色体上 CYP26A1 和 MYOF 基因之间。该关联使用健康与退休研究的数据得到了证实。我们讨论了检测到的 SNP 对人类长寿的生物学相关性。
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本文引用的文献
1
Hidden heterogeneity in Alzheimer's disease: Insights from genetic association studies and other analyses.阿尔茨海默病的潜在异质性：遗传关联研究及其他分析的启示。
Exp Gerontol. 2018 Jul 1;107:148-160. doi: 10.1016/j.exger.2017.10.020. Epub 2017 Oct 26.
2
: an R package for querying web-based annotation tools.一个用于查询基于网络的注释工具的R包。
F1000Res. 2017 Feb 1;6:97. doi: 10.12688/f1000research.10742.2. eCollection 2017.
3
Investigation of the 5q33.3 longevity locus and age-related phenotypes.5q33.3长寿基因座及与年龄相关表型的研究。
Aging (Albany NY). 2017 Jan 13;9(1):247-255. doi: 10.18632/aging.101156.
4
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J Gerontol A Biol Sci Med Sci. 2017 Oct 1;72(10):1401-1406. doi: 10.1093/gerona/glw198.
5
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Am J Hum Genet. 2016 Apr 7;98(4):653-66. doi: 10.1016/j.ajhg.2016.02.012. Epub 2016 Mar 24.
6
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Mech Ageing Dev. 2016 Apr;155:7-9. doi: 10.1016/j.mad.2016.02.010. Epub 2016 Feb 27.
7
Novel loci and pathways significantly associated with longevity.与长寿显著相关的新基因座和通路。
Sci Rep. 2016 Feb 25;6:21243. doi: 10.1038/srep21243.
8
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9
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Nucleic Acids Res. 2016 Jan 4;44(D1):D877-81. doi: 10.1093/nar/gkv1340. Epub 2015 Dec 10.
10
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J Gerontol A Biol Sci Med Sci. 2015 Aug;70(8):971-6. doi: 10.1093/gerona/glv015. Epub 2015 Mar 5.
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