Harris Sarah E, Riggio Valentina, Evenden Louise, Gilchrist Tamara, McCafferty Sarah, Murphy Lee, Wrobel Nicola, Taylor Adele M, Corley Janie, Pattie Alison, Cox Simon R, Martin-Ruiz Carmen, Prendergast James, Starr John M, Marioni Riccardo E, Deary Ian J
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, EH8 9JZ, UK.
Medical Genetics Section, University of Edinburgh Centre for Genomic and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, EH4 2XU, UK.
Aging (Albany NY). 2017 Dec 1;9(12):2489-2503. doi: 10.18632/aging.101333.
Gene expression is influenced by both genetic variants and the environment. As individuals age, changes in gene expression may be associated with decline in physical and cognitive abilities. We measured transcriptome-wide expression levels in lymphoblastoid cell lines derived from members of the Lothian Birth Cohort 1936 at mean ages 70 and 76 years. Changes in gene expression levels were identified for 1,741 transcripts in 434 individuals. Gene Ontology enrichment analysis indicated an enrichment of biological processes involved in the immune system. Transcriptome-wide association analysis was performed for eleven cognitive, fitness, and biomedical aging-related traits at age 70 years (N=665 to 781) and with mortality. Transcripts for genes ( and ) previously identified as being differentially methylated or expressed in smoking or smoking-related cancers were overexpressed in smokers compared to non-smokers and the expression of transcripts for genes ( and ) previously associated with stress response, autoimmune disease and cancer were associated with telomere length. No associations between expression levels and other traits, or mortality were identified.
基因表达受遗传变异和环境的双重影响。随着个体年龄增长，基因表达的变化可能与身体和认知能力的衰退有关。我们测量了来自1936年洛锡安出生队列成员的淋巴母细胞系在平均年龄70岁和76岁时全转录组范围的表达水平。在434名个体中，鉴定出1741个转录本的基因表达水平发生了变化。基因本体富集分析表明免疫系统相关的生物过程得到了富集。对70岁时（N = 665至781）的十一项认知、健康和生物医学衰老相关性状以及死亡率进行了全转录组关联分析。与不吸烟者相比，先前确定在吸烟或吸烟相关癌症中存在差异甲基化或表达的基因（和）的转录本在吸烟者中过度表达，并且先前与应激反应、自身免疫性疾病和癌症相关的基因（和）的转录本表达与端粒长度相关。未发现表达水平与其他性状或死亡率之间存在关联。
