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Epigenome-wide analysis in newborn blood spots from monozygotic twins discordant for cerebral palsy reveals consistent regional differences in DNA methylation

Overview of attention for article published in Clinical Epigenetics, February 2018
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  • In the top 5% of all research outputs scored by Altmetric
  • Among the highest-scoring outputs from this source (#33 of 944)
  • High Attention Score compared to outputs of the same age (91st percentile)

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2 news outlets
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15 tweeters

Citations

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20 Dimensions

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54 Mendeley
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Title
Epigenome-wide analysis in newborn blood spots from monozygotic twins discordant for cerebral palsy reveals consistent regional differences in DNA methylation
Published in
Clinical Epigenetics, February 2018
DOI 10.1186/s13148-018-0457-4
Pubmed ID
Authors

Namitha Mohandas, Sebastian Bass-Stringer, Jovana Maksimovic, Kylie Crompton, Yuk J. Loke, Janet Walstab, Susan M. Reid, David J. Amor, Dinah Reddihough, Jeffrey M. Craig

Abstract

Cerebral palsy (CP) is a clinical description for a group of motor disorders that are heterogeneous with respect to causes, symptoms and severity. A diagnosis of CP cannot usually be made at birth and in some cases may be delayed until 2-3 years of age. This limits opportunities for early intervention that could otherwise improve long-term outcomes. CP has been recorded in monozygotic twins discordant for the disorder, indicating a potential role of non-genetic factors such as intrauterine infection, hypoxia-ischaemia, haemorrhage and thrombosis. The aim of this exploratory study was to utilise the discordant monozygotic twin model to understand and measure epigenetic changes associated with the development of CP. We performed a genome-wide analysis of DNA methylation using the Illumina Infinium Human Methylation 450 BeadChip array with DNA from newborn blood spots of 15 monozygotic twin pairs who later became discordant for CP. Quality control and data preprocessing were undertaken using theminfiR package. Differential methylation analysis was performed using the remove unwanted variation (RUVm) method, taking twin pairing into account in order to identify CP-specific differentially methylated probes (DMPs), andbumphunterwas performed to identify differentially methylated regions (DMRs). We identified 33 top-ranked DMPs based on a nominalpvalue cut-off ofp < 1 × 10-4and two DMRs (p < 1 × 10-3) associated with CP. The top-ranked probes related to 25 genes includingHNRNPL,RASSF5,CD3DandKALRNinvolved in immune signalling pathways, in addition toTBC1D24,FBXO9andVIPR2previously linked to epileptic encephalopathy. Gene ontology and pathway analysis of top-ranked DMP-associated genes revealed enrichment of inflammatory signalling pathways, regulation of cytokine secretion and regulation of leukocyte-mediated immunity. We also identified two top-ranked DMRs including one on chromosome 6 within the promoter region ofLTAgene encoding tumour necrosis factor-beta (TNF-β), an important regulator of inflammation and brain development. The second was within the transcription start site of theLIME1gene, which plays a key role in inflammatory pathways such as MAPK signalling. CP-specific differential DNA methylation within one of our two top DMRs was validated using an independent platform, MassArray EpiTyper. Ours is the first epigenome-wide association study of CP in disease-discordant monozygotic twin pairs and suggests a potential role for immune dysfunction in this condition.

Twitter Demographics

The data shown below were collected from the profiles of 15 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 54 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 54 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 12 22%
Student > Master 7 13%
Researcher 5 9%
Student > Postgraduate 4 7%
Student > Doctoral Student 4 7%
Other 11 20%
Unknown 11 20%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 12 22%
Nursing and Health Professions 8 15%
Neuroscience 5 9%
Medicine and Dentistry 5 9%
Psychology 3 6%
Other 8 15%
Unknown 13 24%

Attention Score in Context

This research output has an Altmetric Attention Score of 29. 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 15 May 2018.
All research outputs
#843,254
of 17,418,198 outputs
Outputs from Clinical Epigenetics
#33
of 944 outputs
Outputs of similar age
#24,425
of 284,506 outputs
Outputs of similar age from Clinical Epigenetics
#1
of 1 outputs
Altmetric has tracked 17,418,198 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 95th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 944 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.1. This one has done particularly well, scoring higher than 96% 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 284,506 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 91% of its contemporaries.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them