Altered DNA methylation associated with a translocation linked to major mental illness

Published online March, 2018
Daniel L. McCartney, Rosie M. Walker, Stewart W. Morris, Susan M. Anderson, Barbara J. Duff, Riccardo E. Marioni, J. Kirsty Millar, Shane E. McCarthy, Niamh M. Ryan, Stephen M. Lawrie, Andrew R. Watson, Douglas H. R. Blackwood, Pippa A. Thomson, Andrew M. McIntosh, W. Richard McCombie, David J. Porteous & Kathryn L. Evans
npj Schizophrenia volume 4, Article number: 5 (2018)
Recent work has highlighted a possible role for altered epigenetic modifications, including differential DNA methylation, in susceptibility to psychiatric illness. Here, we investigate blood-based DNA methylation in a large family where a balanced translocation between chromosomes 1 and 11 shows genome-wide significant linkage to psychiatric illness. Genome-wide DNA methylation was profiled in whole-blood-derived DNA from 41 individuals using the Infinium HumanMethylation450 BeadChip (Illumina Inc., San Diego, CA). We found significant differences in DNA methylation when translocation carriers (n = 17) were compared to related non-carriers (n = 24) at 13 loci. All but one of the 13 significant differentially methylated positions (DMPs) mapped to the regions surrounding the translocation breakpoints. Methylation levels of five DMPs were associated with genotype at SNPs in linkage disequilibrium with the translocation. Two of the five genes harbouring significant DMPs, DISC1 and DUSP10, have been previously shown to be differentially methylated in schizophrenia. Gene Ontology analysis revealed enrichment for terms relating to neuronal function and neurodevelopment among the genes harbouring the most significant DMPs. Differentially methylated region (DMR) analysis highlighted a number of genes from the MHC region, which has been implicated in psychiatric illness previously through genetic studies. We show that inheritance of a translocation linked to major mental illness is associated with differential DNA methylation at loci implicated in neuronal development/function and in psychiatric illness. As genomic rearrangements are over-represented in individuals with psychiatric illness, such analyses may be valuable more widely in the study of these conditions.
This study links to Lyme/MSIDS in more than one way.
  • First, many Lyme/MSIDS patients have methylation problems and can not detox properly.  Imagine a kitty litter box that never gets cleaned out.  That’s what happens inside a body that can’t clear itself of debris.
  • Second, many Lyme/MSIDS patients have mental health issues:  (5-Part Series showing how Lyme/MSIDS manifests)
  • Third, Lyme/MSIDS mimics methylation problems and vice versa.  One of the challenges of treatment is teasing out what is active infection(s) and what is a methylation problem.  Pharmacist Suzy Cohen states 100’s of diseases are the result of methylation problems, including Lyme, chronic viral infections, schizophrenia, Dementia/Alzheimer’s, addictive behavior, insomnia, cancer, and more.

While methylation problems do not directly cause Lyme (it is caused by a pleomorphic bacteria called borrelia) it causes severe symptoms due to the inability to clear infections & their by-products, as well as repairing the damage they cause.

Methylation also helps you clear toxins such as hormones from chemicals, and rogue neurotransmitters that can cause seizures, anxiety, rage, and insomnia.

If you are extremely sensitive to medicine you probably have a methylation problem.  Cohen also states that while some of this stems from genetics, there are other reasons for it such as a lack of the following vitamins:

  • Zinc
  • B2/riboflavin
  • Magnesium
  • B6/pyridoxine
  • B12/methylcobalamin
  • Folate (from food or folinic acid)

1) Poor diet, poor probiotic status, digestive issues, medications, medical conditions like Crohn’s or Celiac, and other genetic traits may cause any or all of these nutrient deficiencies.

2) Xenobiotics – which are chemicals found in our air, water, food, home, work, schools, parks, beds, cosmetics and more.

3) Taking medications that are drug muggers that deplete you of the nutrients in #1 above. Some of the worst offenders (in terms of stealing your methylation nutrients) are methotrexate, metformin, antacids, acid blockers, proton pump inhibitors, corticosteroids, estrogen-containing drugs and nitrous oxide.

4) Drinking alcohol will pretty much shut down your methylation and wipe out your glutathione stores.

5) Green coffee bean extract is incredibly high in catechols and those use up your methylation pathway nutrients fast!

7) If you have Lyme disease, and many people do whether they know it or not, the Borrelia burgdorferi germ uses up all your magnesium (this supplement is a unique and highly absorbable form) to make biofilms and hide. Low mag reduces your ability to methylate. As an aside, this explains why some ‘Lymies’ have bad reactions during antibiotic treatment. Those drugs kill the organism but then your body is faced with poison such as ‘dead bug parts’ as well as ammonia which spikes when Borrelia dies off. Point is, you can’t remove easily the toxins from your body and it backs up in your system (by christopher at If this is you, then use really low doses if you have to take antibiotics, until you’ve opened up your methylation (and other detoxification) pathways.

8) If you take nutrients that deplete methyl groups (like high dose niacin, or the prescription version of that called Slo-Niacin and Niaspan).

9) Heavy metals (think mercury in your diet, or your teeth) or lead in your bloodstream, cadmium if you smoke, high copper, arsenic, etc.

10) High levels of acetylaldehyde, this is a potent neurotoxin released by Candida, and also a by-product of drinking alcohol (even red wine). Don’t drink if you’re a poor methylator. Most of you know who you are, meaning you are a lightweight when it comes to alcohol. Yep, it is likely you are a poor methylator. I will share more about the Candida toxin known as “acetylaldehyde” shortly.

12) Anxiety or a lot of stress. I’m not sure why, but a pessimist or “I can’t do it” kind of outlook seems to make things worse. I think it has to do with your belief systems and how they impact your genes. In my summary, I’ll give you some links to an author and lecturer that has clues on how to change your outlook. (Dr. Bruce Lipton).

Please see Cohen’s article for options if you suspect a methylation defect: