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Genetically defined elevated homocysteine levels do not result in widespread changes of DNA methylation in leukocytes

Overview of attention for article published in PLOS ONE, October 2017
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Title
Genetically defined elevated homocysteine levels do not result in widespread changes of DNA methylation in leukocytes
Published in
PLOS ONE, October 2017
DOI 10.1371/journal.pone.0182472
Pubmed ID
Authors

Pooja R. Mandaviya, Roby Joehanes, Dylan Aïssi, Brigitte Kühnel, Riccardo E. Marioni, Vinh Truong, Lisette Stolk, Marian Beekman, Marc Jan Bonder, Lude Franke, Christian Gieger, Tianxiao Huan, M. Arfan Ikram, Sonja Kunze, Liming Liang, Jan Lindemans, Chunyu Liu, Allan F. McRae, Michael M. Mendelson, Martina Müller-Nurasyid, Annette Peters, P. Eline Slagboom, John M. Starr, David-Alexandre Trégouët, André G. Uitterlinden, Marleen M. J. van Greevenbroek, Diana van Heemst, Maarten van Iterson, Philip S. Wells, Chen Yao, Ian J. Deary, France Gagnon, Bastiaan T. Heijmans, Daniel Levy, Pierre-Emmanuel Morange, Melanie Waldenberger, Sandra G. Heil, Joyce B. J. van Meurs

Abstract

DNA methylation is affected by the activities of the key enzymes and intermediate metabolites of the one-carbon pathway, one of which involves homocysteine. We investigated the effect of the well-known genetic variant associated with mildly elevated homocysteine: MTHFR 677C>T independently and in combination with other homocysteine-associated variants, on genome-wide leukocyte DNA-methylation. Methylation levels were assessed using Illumina 450k arrays on 9,894 individuals of European ancestry from 12 cohort studies. Linear-mixed-models were used to study the association of additive MTHFR 677C>T and genetic-risk score (GRS) based on 18 homocysteine-associated SNPs, with genome-wide methylation. Meta-analysis revealed that the MTHFR 677C>T variant was associated with 35 CpG sites in cis, and the GRS showed association with 113 CpG sites near the homocysteine-associated variants. Genome-wide analysis revealed that the MTHFR 677C>T variant was associated with 1 trans-CpG (nearest gene ZNF184), while the GRS model showed association with 5 significant trans-CpGs annotated to nearest genes PTF1A, MRPL55, CTDSP2, CRYM and FKBP5. Our results do not show widespread changes in DNA-methylation across the genome, and therefore do not support the hypothesis that mildly elevated homocysteine is associated with widespread methylation changes in leukocytes.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 39 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 39 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 6 15%
Student > Ph. D. Student 5 13%
Student > Bachelor 5 13%
Professor > Associate Professor 3 8%
Student > Master 3 8%
Other 8 21%
Unknown 9 23%
Readers by discipline Count As %
Medicine and Dentistry 9 23%
Biochemistry, Genetics and Molecular Biology 8 21%
Agricultural and Biological Sciences 4 10%
Nursing and Health Professions 3 8%
Psychology 2 5%
Other 3 8%
Unknown 10 26%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 3. 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 05 June 2018.
All research outputs
#13,336,880
of 23,007,053 outputs
Outputs from PLOS ONE
#105,878
of 196,140 outputs
Outputs of similar age
#160,860
of 328,606 outputs
Outputs of similar age from PLOS ONE
#1,715
of 3,581 outputs
Altmetric has tracked 23,007,053 research outputs across all sources so far. This one is in the 41st percentile – i.e., 41% of other outputs scored the same or lower than it.
So far Altmetric has tracked 196,140 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 15.1. This one is in the 44th percentile – i.e., 44% of its peers scored the same or lower than it.
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 328,606 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 50% of its contemporaries.
We're also able to compare this research output to 3,581 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 50% of its contemporaries.