Åberg and van den Oord (
1
) raised several important issues that keep the field of human methylation research
divided and, indeed, deserve to be discussed explicitly. First, the authors suggest
that two factors might explain similarity in methylation between central nervous system
cells and cells sampled in the periphery: changes in the germ line or changes in early
embryogenesis. Second, they suggest that there are two alternatives for measuring
methylation with peripheral indexes: lymphoblast cell lines or WB. Finally, they conclude
that, given the choice between WB and high-pass lymphoblast cell lines, WB would be
superior. We disagree with both the assumptions and the conclusion, and we briefly
address each of the points below.To read this article in full you will need to make a payment
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References
- Epstein–Barr virus transformed DNA as a source of false positive findings in methylation studies of psychiatric conditions.Biol Psychiatry. 2011; 70: e25-e26
- Methylation matters: Interaction between methylation density and serotonin transporter genotype predicts unresolved loss or trauma.Biol Psychiatry. 2010; 68: 405-407
- Differential gene expression of blood-derived cell lines in familial combined hyperlipidemia.Arterioscler Thromb Vasc Biol. 2004; 24: 2149-2154
- EBV transformation and cell culturing destabilizes DNA methylation in human lymphoblastoid cell lines.Genomics. 2009; 95: 73-83
- Extreme clonality in lymphoblastoid cell lines with implications for allele specific expression analyses.PLoS ONE. 2008; 3: e2966
- Comprehensive methylome map of lineage commitment from haematopoietic progenitors.Nature. 2010; 467: 338-342
- Analysis of whole genome biomarker expression in blood and brain.Am J Med Genet B Neuropsychiatr Genet. 2010; 153B: 919-936
Article info
Publication history
Published online: April 21, 2011
Footnotes
The authors report no biomedical financial interests or potential conflicts of interest. On behalf of Dr. Philibert, the University of Iowa has filed intellectual property claims with respect to the serotonin transport protein. Dr. Philibert is a potential royalty holder on that application.
Please also see associated correspondence, doi:10.1016/j.biopsych.2011.01.042.
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Copyright
© 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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- Epstein–Barr Virus Transformed DNA as a Source of False Positive Findings in Methylation Studies of Psychiatric ConditionsBiological PsychiatryVol. 70Issue 5
- PreviewMethylation patterns are tissue-specific (1). Methylation studies are therefore ideally performed in the tissue that is directly related to the disease of interest. However, for psychiatric conditions, it is not feasible to obtain brain tissue from (living) patients. In these instances, whole blood might serve as a proxy. There is indeed ample evidence suggesting that methylation signatures might not be limited to the affected tissue and are detectible in peripheral biofluids. One example involves the loss of imprinting of insulin-like growth factor-2, one of the best-studied epimutations that is associated with increased risk of colorectal cancer (2).
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