DNA methylation linked to all-cause mortality in older people: An epigenome-wide association study.

Research output: Contribution to conference without publisher/journalPosterResearchpeer-review

Abstract

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.
Original languageEnglish
Publication dateMar 2018
Publication statusPublished - Mar 2018
EventCLEPSO: Clinical Epigenetics Society Meeting 2018 - Düsseldorf City-Hostel, Düsseldorf, Germany
Duration: 8. Mar 20189. Mar 2018
http://www.clinical-epigenetics-society.org/meeting-2018x

Conference

ConferenceCLEPSO: Clinical Epigenetics Society Meeting 2018
LocationDüsseldorf City-Hostel
CountryGermany
CityDüsseldorf
Period08/03/201809/03/2018
Internet address

Fingerprint

DNA Methylation
G-Protein-Coupled Receptors
Proportional Hazards Models
Epigenomics
Skeleton
Cohort Studies
Muscles

Keywords

  • older poeple
  • Epigenome-wide association study
  • EWAS
  • Survival Analysis
  • DNA methylation
  • gene set enrichment analysis
  • GSEA
  • de-novo pathway analysis
  • Mortality

Cite this

Lund, J., Baumbach, J., & Tan, Q. (2018). DNA methylation linked to all-cause mortality in older people: An epigenome-wide association study.. Poster session presented at CLEPSO: Clinical Epigenetics Society Meeting 2018, Düsseldorf, Germany.
Lund, Jesper ; Baumbach, Jan ; Tan, Qihua. / DNA methylation linked to all-cause mortality in older people: An epigenome-wide association study. Poster session presented at CLEPSO: Clinical Epigenetics Society Meeting 2018, Düsseldorf, Germany.
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abstract = "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.",
keywords = "older poeple, Epigenome-wide association study, EWAS, Survival Analysis, DNA methylation, gene set enrichment analysis, GSEA, de-novo pathway analysis, Mortality",
author = "Jesper Lund and Jan Baumbach and Qihua Tan",
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Lund, J, Baumbach, J & Tan, Q 2018, 'DNA methylation linked to all-cause mortality in older people: An epigenome-wide association study.' CLEPSO: Clinical Epigenetics Society Meeting 2018, Düsseldorf, Germany, 08/03/2018 - 09/03/2018, .

DNA methylation linked to all-cause mortality in older people: An epigenome-wide association study. / Lund, Jesper; Baumbach, Jan; Tan, Qihua.

2018. Poster session presented at CLEPSO: Clinical Epigenetics Society Meeting 2018, Düsseldorf, Germany.

Research output: Contribution to conference without publisher/journalPosterResearchpeer-review

TY - CONF

T1 - DNA methylation linked to all-cause mortality in older people: An epigenome-wide association study.

AU - Lund, Jesper

AU - Baumbach, Jan

AU - Tan, Qihua

PY - 2018/3

Y1 - 2018/3

N2 - 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.

AB - 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.

KW - older poeple

KW - Epigenome-wide association study

KW - EWAS

KW - Survival Analysis

KW - DNA methylation

KW - gene set enrichment analysis

KW - GSEA

KW - de-novo pathway analysis

KW - Mortality

M3 - Poster

ER -

Lund J, Baumbach J, Tan Q. DNA methylation linked to all-cause mortality in older people: An epigenome-wide association study.. 2018. Poster session presented at CLEPSO: Clinical Epigenetics Society Meeting 2018, Düsseldorf, Germany.