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DNA methylation patterns associated with oxidative stress in an ageing population

Overview of attention for article published in BMC Medical Genomics, November 2016
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (80th percentile)

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DNA methylation patterns associated with oxidative stress in an ageing population
Published in
BMC Medical Genomics, November 2016
DOI 10.1186/s12920-016-0235-0
Pubmed ID

Åsa K. Hedman, Mihkel Zilmer, Johan Sundström, Lars Lind, Erik Ingelsson


Oxidative stress has been related to type 2 diabetes (T2D) and cardiovascular disease (CVD), the leading global cause of death. Contributions of environmental factors such as oxidative stress on complex traits and disease may be partly mediated through changes in epigenetic marks (e.g. DNA methylation). Studies relating differential methylation with intermediate phenotypes and disease endpoints may be useful in identifying additional candidate genes and mechanisms involved in disease. To investigate the role of epigenetic variation in oxidative stress marker levels and subsequent development of CVD and T2D, we performed analyses of genome-wide DNA methylation in blood, ten markers of oxidative stress (total glutathione [TGSH], reduced glutathione [GSH], oxidised glutathione [GSSG], GSSG to GSH ratio, homocysteine [HCY], oxidised low-density lipoprotein (oxLDL), antibodies against oxLDL [OLAB], conjugated dienes [CD], baseline conjugated dienes [BCD]-LDL and total antioxidant capacity [TAOC]) and incident disease in up to 966 age-matched individuals. In total, we found 66 cytosine-guanine (CpG) sites associated with one or more oxidative stress markers (false discovery rate [FDR] <0.05). These sites were enriched in regulatory regions of the genome. Genes annotated to CpG sites showed enrichment in annotation clusters relating to phospho-metabolism and proteins with pleckstrin domains. We investigated the contribution of oxidative stress-associated CpGs to development of cardiometabolic disease. Methylation variation at CpGs in the 3'-UTR of HIST1H4D (cg08170869; histone cluster 1, H4d) and in the body of DVL1 (cg03465880; dishevelled-1) were associated with incident T2D events during 10 years of follow-up (all permutation p-values <0.01), indicating a role of epigenetic regulation in oxidative stress processes leading to development or progression of diabetes. Methylation QTL (meQTL) analysis showed significant associations with genetic sequence variants in cis at 28 (42%) of oxidative stress phenotype-associated sites (FDR < 0.05). Integrating cis-meQTLs with genotype-phenotype associations indicated that genetic effects on oxidative stress phenotype at one locus (cg07547695; BCL2L11) may be mediated through DNA methylation. In conclusion, we report novel associations of DNA methylation with oxidative stress, some of which also show evidence of a relation with T2D incidence.

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Mendeley readers

The data shown below were compiled from readership statistics for 48 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 48 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 12 25%
Researcher 6 13%
Student > Master 4 8%
Student > Doctoral Student 4 8%
Other 4 8%
Other 11 23%
Unknown 7 15%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 17 35%
Agricultural and Biological Sciences 11 23%
Medicine and Dentistry 4 8%
Neuroscience 2 4%
Computer Science 1 2%
Other 5 10%
Unknown 8 17%

Attention Score in Context

This research output has an Altmetric Attention Score of 9. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 22 July 2017.
All research outputs
of 14,362,664 outputs
Outputs from BMC Medical Genomics
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Outputs of similar age
of 349,674 outputs
Outputs of similar age from BMC Medical Genomics
of 4 outputs
Altmetric has tracked 14,362,664 research outputs across all sources so far. Compared to these this one has done well and is in the 84th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 756 research outputs from this source. They receive a mean Attention Score of 4.6. This one has done well, scoring higher than 84% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 349,674 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 80% of its contemporaries.
We're also able to compare this research output to 4 others from the same source and published within six weeks on either side of this one. This one has scored higher than 2 of them.