Research Paper Volume 9, Issue 12 pp 2489—2503
Age-related gene expression changes, and transcriptome wide association study of physical and cognitive aging traits, in the Lothian Birth Cohort 1936
- 1 Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, EH8 9JZ, UK
- 2 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
- 3 The Roslin Institute and R(D)SVS, University of Edinburgh, Easter Bush Campus, Midlothian, EH25 9RG, UK
- 4 Edinburgh Clinical Research Facility, University of Edinburgh, Western General Hospital, Edinburgh, EH4 2XU, UK
- 5 Department of Psychology, University of Edinburgh, Edinburgh, EH8 9JZ, UK
- 6 Institute for Ageing, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5PL, UK
- 7 Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, EH8 9JZ, UK
- 8 Queensland Brain Institute, The University of Queensland, Brisbane 4072, QLD, Australia
Received: August 14, 2017 Accepted: November 26, 2017 Published: December 1, 2017
https://doi.org/10.18632/aging.101333How to Cite
Abstract
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 (F2RL3, EMILIN1 and CDC42BPA) 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 (HERPUD1, GAB2, FAM167A and GLS) 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.