人类外周血中年龄的转录图谱。
The transcriptional landscape of age in human peripheral blood.
作者信息
Peters Marjolein J, Joehanes Roby, Pilling Luke C, Schurmann Claudia, Conneely Karen N, Powell Joseph, Reinmaa Eva, Sutphin George L, Zhernakova Alexandra, Schramm Katharina, Wilson Yana A, Kobes Sayuko, Tukiainen Taru, Ramos Yolande F, Göring Harald H H, Fornage Myriam, Liu Yongmei, Gharib Sina A, Stranger Barbara E, De Jager Philip L, Aviv Abraham, Levy Daniel, Murabito Joanne M, Munson Peter J, Huan Tianxiao, Hofman Albert, Uitterlinden André G, Rivadeneira Fernando, van Rooij Jeroen, Stolk Lisette, Broer Linda, Verbiest Michael M P J, Jhamai Mila, Arp Pascal, Metspalu Andres, Tserel Liina, Milani Lili, Samani Nilesh J, Peterson Pärt, Kasela Silva, Codd Veryan, Peters Annette, Ward-Caviness Cavin K, Herder Christian, Waldenberger Melanie, Roden Michael, Singmann Paula, Zeilinger Sonja, Illig Thomas, Homuth Georg, Grabe Hans-Jörgen, Völzke Henry, Steil Leif, Kocher Thomas, Murray Anna, Melzer David, Yaghootkar Hanieh, Bandinelli Stefania, Moses Eric K, Kent Jack W, Curran Joanne E, Johnson Matthew P, Williams-Blangero Sarah, Westra Harm-Jan, McRae Allan F, Smith Jennifer A, Kardia Sharon L R, Hovatta Iiris, Perola Markus, Ripatti Samuli, Salomaa Veikko, Henders Anjali K, Martin Nicholas G, Smith Alicia K, Mehta Divya, Binder Elisabeth B, Nylocks K Maria, Kennedy Elizabeth M, Klengel Torsten, Ding Jingzhong, Suchy-Dicey Astrid M, Enquobahrie Daniel A, Brody Jennifer, Rotter Jerome I, Chen Yii-Der I, Houwing-Duistermaat Jeanine, Kloppenburg Margreet, Slagboom P Eline, Helmer Quinta, den Hollander Wouter, Bean Shannon, Raj Towfique, Bakhshi Noman, Wang Qiao Ping, Oyston Lisa J, Psaty Bruce M, Tracy Russell P, Montgomery Grant W, Turner Stephen T, Blangero John, Meulenbelt Ingrid, Ressler Kerry J, Yang Jian, Franke Lude, Kettunen Johannes, Visscher Peter M, Neely G Gregory, Korstanje Ron, Hanson Robert L, Prokisch Holger, Ferrucci Luigi, Esko Tonu, Teumer Alexander, van Meurs Joyce B J, Johnson Andrew D
机构信息
Department of Internal Medicine, Erasmus Medical Centre Rotterdam, Rotterdam 3000CA, The Netherlands.
The National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, Massachusetts 01702, USA.
出版信息
Nat Commun. 2015 Oct 22;6:8570. doi: 10.1038/ncomms9570.
Disease incidences increase with age, but the molecular characteristics of ageing that lead to increased disease susceptibility remain inadequately understood. Here we perform a whole-blood gene expression meta-analysis in 14,983 individuals of European ancestry (including replication) and identify 1,497 genes that are differentially expressed with chronological age. The age-associated genes do not harbor more age-associated CpG-methylation sites than other genes, but are instead enriched for the presence of potentially functional CpG-methylation sites in enhancer and insulator regions that associate with both chronological age and gene expression levels. We further used the gene expression profiles to calculate the 'transcriptomic age' of an individual, and show that differences between transcriptomic age and chronological age are associated with biological features linked to ageing, such as blood pressure, cholesterol levels, fasting glucose, and body mass index. The transcriptomic prediction model adds biological relevance and complements existing epigenetic prediction models, and can be used by others to calculate transcriptomic age in external cohorts.
疾病发病率随年龄增长而增加，但导致疾病易感性增加的衰老分子特征仍未得到充分理解。在此，我们对14983名欧洲血统个体进行了全血基因表达荟萃分析（包括重复验证），并鉴定出1497个随实足年龄差异表达的基因。与年龄相关的基因并不比其他基因含有更多与年龄相关的CpG甲基化位点，而是在增强子和绝缘子区域富含潜在功能性CpG甲基化位点，这些位点与实足年龄和基因表达水平均相关。我们进一步利用基因表达谱计算个体的“转录组年龄”，并表明转录组年龄与实足年龄之间的差异与衰老相关的生物学特征有关，如血压、胆固醇水平、空腹血糖和体重指数。转录组预测模型增加了生物学相关性，补充了现代表观遗传预测模型，可供他人用于计算外部队列中的转录组年龄。
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