Tuesday, June 23, 2009

Genetics, CFS and Depression

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Genomics. 2009 Jun 17.

An Integrated Approach to Infer Causal
Associations among Gene Expression,
Genotype Variation, and Disease.

Lee E, Cho S, Kim K, Park T.

Interdisciplinary Program in Bioinformatics, Seoul
National University, Seoul, Korea.

Gene expression data and genotype variation data
are now capable of providing genome-wide patterns
across many different clinical conditions.

However, the separate analysis of these data has
limitations in elucidating the complex network of
gene interactions underlying complex traits, such as
common human diseases.

More information about the identity of key driver
genes of common diseases comes from integrating
these two heterogeneous types of data.

We developed a two-step procedure to characterize
complex diseases by integrating genotype variation
data and gene expression data.

The first step elucidates the causal relationship
among genetic variation, gene expression level, and

Based on the causal relationship determined at the
first step, the second step identifies significant gene
expression traits whose effects on disease status or
whose responses to disease status are modified by
the specific genotype variation.

For the selected significant genes, a pathway
enrichment analysis can be performed to identify the
genetic mechanism of a complex disease.

The proposed two-step procedure was shown to be
an effective method for integrating three different
levels of data, i.e., genotype variation, gene
expression and disease status.

By applying the proposed procedure to a chronic
fatigue syndrome (CFS) dataset, we identified a list
of potential causal genes for CFS, and found an
evidence for difference in genetic mechanisms of the
etiology between CFS without 'a major depressive
disorder with melancholic features' (CFS) and CFS
with 'a major depressive disorder with melancholic
features' (CFS-MDD/m).

Especially, the SNPs within NR3C1 gene were shown
to differently influence the susceptibility of
developing CFS and CFS-MDD/m through integrative
action with gene expression levels.

PMID: 19540336 [PubMed - as supplied by publisher]
* * *
I wonder if "CFS with a major depressive disorder" is actually just a case of depression sloppily misdiagnosed as CFS?
Under the original diagnostic criteria, anyone with a history of depression was precluded from receiving a CFS diagnosis.  CDC's repeated revisions of the diagnostic criteria have now blurred the line to the point that their questionnaires are including people with depression and other emotional disorders, and excluding patients with severe CFS.


Mama said...

No, I don't think MDD is being misdiagnosed as CFS. (Quite the opposite). There are physical symptoms of CFS that would not be part of MDD (Including orthostatic intolerance, sensory overload, heat intolerance, cold intolerance, post-exertion malaise). In fact, many people think you can exercise your way out if depression, which would be contraindicated in CFS.

Anonymous said...

Totally agree with Mama. There are now something like 88 genes associated with CFIDS, many of them mitochondria related and many with different cancers sitting on them. It is also now believed that this is indeed a "genetic" disease and may possibly be contagious. Explain how spouses get sick from CFIDS when they are not related? Explain clusters like that in Incline Village and the London Royal Hospital, the Florida Punto Vista outbreak, and so on.
I have had CFIDS and FM for 16 years now. Four years ago my healthy husband came down with many of the symptoms of CFIDS. He lays on the couch much of the day and night and this used to be a hardworking and rather healthy man. I think I GAVE him the CFIDS. Neither one of us is clinically depressed except for being mad as H-ll about being so sick, exhausted and having our lives taken from us. I guess that would be more than enough to be situationally depressed about.

CFS Facts said...

The only relative with CFS is someone I share no blood with (related by marriage), so I also quibble with the notion of congenital. The pro-genetic crowd point out that "it runs in families" as if they never heard of a family passing a flu bug around.

Dr. Fujioka points out that it's been known for years that viruses can re-program your DNA, and I suspect that's where the gene damage comes from.