Dataset Information

DNA Methylation and All-Cause Mortality in Middle-Aged and Elderly Danish Twins.

ABSTRACT: Several studies have linked DNA methylation at individual CpG sites to aging and various diseases. Recent studies have also identified single CpGs whose methylation levels are associated with all-cause mortality. In this study, we perform an epigenome-wide study of the association between CpG methylation and mortality in a population of 435 monozygotic twin pairs from three Danish twin studies. The participants were aged 55-90 at the time of blood sampling and were followed for up to 20 years. We validated our results by comparison with results from a British and a Swedish cohort, as well as results from the literature. We identified 2806 CpG sites associated with mortality (false discovery rate ( FDR ) < 0.05 ), of which 24 had an association p-value below 10 - 7 . This was confirmed by intra-pair comparison controlling for confounding effects. Eight of the 24 top sites could be validated in independent datasets or confirmed by previous studies. For all these eight sites, hypomethylation was associated with poor survival prognosis, and seven showed monozygotic correlations above 35%, indicating a potential moderate to strong heritability, but leaving room for substantial shared or unique environmental effects. We also set up a predictor for mortality using least absolute shrinkage and selection operator (LASSO) regression. The predictor showed good performance on the Danish data under cross-validation, but did not perform very well in independent samples.

SUBMITTER: Svane AM

PROVIDER: S-EPMC5852574 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Publications

DNA Methylation and All-Cause Mortality in Middle-Aged and Elderly Danish Twins.

Svane Anne Marie AM Soerensen Mette M Lund Jesper J Tan Qihua Q Jylhävä Juulia J Wang Yunzhang Y Pedersen Nancy L NL Hägg Sara S Debrabant Birgit B Deary Ian J IJ Christensen Kaare K Christiansen Lene L Hjelmborg Jacob B JB

Genes 20180208 2

Several studies have linked DNA methylation at individual CpG sites to aging and various diseases. Recent studies have also identified single CpGs whose methylation levels are associated with all-cause mortality. In this study, we perform an epigenome-wide study of the association between CpG methylation and mortality in a population of 435 monozygotic twin pairs from three Danish twin studies. The participants were aged 55-90 at the time of blood sampling and were followed for up to 20 years. W ...[more]

PMID: 29419728

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Project description:BACKGROUND:Transient cognitive impairment is common in adult patients of all ages following anaesthesia and surgery. Apolipoprotein E (APOE) ?4 carriers may have a larger deterioration in short-term cognitive function after major surgery compared with APOE ?4 noncarriers. OBJECTIVES:The aim was to examine the effect of APOE ?4 on the association between exposure to surgery and anaesthesia, and subsequent cognitive functioning. A more pronounced deterioration in cognitive function in APOE ?4 carriers was hypothesised. DESIGN:An observational cross-sectional and a 6 to 10 years longitudinal twin cohort design. SETTING:Survey and register study of 2936 Danish twins aged 45 to 92 years. MAIN OUTCOME MEASURES:Cognitive function was assessed using five age-sensitive cognitive tests. In the cross-sectional study, we compared twins exposed to surgery with a reference group (unexposed). Linear regression models were used adjusting for sex and age and stratified by APOE ?4 carrier status. In the longitudinal cognitive follow-up study 1671 twins participated. Intrapair analyses were also performed using 70 same-sexed twin pairs concordant for APOE ?4 carrier status, but discordant for major surgery. RESULTS:APOE ?4 carriers had lower cognitive scores compared with noncarriers, and this was statistically significant in elderly twins 70+ years of age (mean difference, -0.67; 95% CI, -1.14 to -0.17). There was no significant impact on cognitive function after surgery according to APOE ?4 carrier status in the cross-sectional study. Similarly, there was no APOE ?4 modification in the longitudinal study. Also, in the intrapair analyses no evidence was found of lower cognitive score after major surgery compared with the nonexposed cotwins among APOE ?4 carriers. CONCLUSION:No evidence was found of more pronounced long-term deterioration in cognitive function after surgery among APOE ?4 carriers, but elderly APOE ?4 carriers in general performed worse on the cognitive tests than noncarriers.

Dataset Information

DNA Methylation and All-Cause Mortality in Middle-Aged and Elderly Danish Twins.

Publications

DNA Methylation and All-Cause Mortality in Middle-Aged and Elderly Danish Twins.

Similar Datasets

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