The risk of all-cause mortality includes demographic, epidemiological and clinical factors. At the molecular level, epigenetic mechanisms have been shown to be involved. Using genome-wide DNA methylation data from large-scale cohort studies of older Scottish individuals accompanied by survival information, we performed an epigenome-wide association analysis to identify DNA methylation sites related to all-cause mortality and verified them using data on Danish twins. By fitting the Cox proportional hazard models, we identified 2,552 CpG sites with a genome-wide significance of FDR < 0.05. Among them, 1,403 CpGs positively and 1,149 negatively correlated with respect to mortality. Comparing with the results from the Danish twin cohorts which revealed 2,806 genome-wide significant CpGs, we found 330 overlaps at gene-level. In addition, we performed gene set enrichment analyses for genes linked to significant CpGs and found 41 and 49 gene-sets over-represented respectively by genes linked to CpGs showing positive and negative correlation with mortality, verified in either Danish twins or by a recently published study on aging. These gene-sets are dominated by pathways related to cell-cell signaling, extracellular matrix, neurological functioning, and G protein-coupled receptors. In addition, we performed de-novo pathway enrichment based on the verified genes and extracted the top 20 largest pathways found. Aggregating the top non-exception genes in the enriched pathways, we find a total of 118 unique genes, among these, we found 26 (22%) linked to neuronal, 21 (17.8%) linked to muscle skeleton, and 11 (9.3%) linked to cancerous disorders. We report the largest pathway with 81 nodes as a candidate pathway for further investigation.
|Status||Udgivet - mar. 2018|
|Begivenhed||CLEPSO: Clinical Epigenetics Society Meeting 2018 - Düsseldorf City-Hostel, Düsseldorf, Tyskland|
Varighed: 8. mar. 2018 → 9. mar. 2018
|Konference||CLEPSO: Clinical Epigenetics Society Meeting 2018|
|Periode||08/03/2018 → 09/03/2018|