Re: April 21, 2006: Fatigue gene isolated

[Guest guest]

Have to add that it annoys me how the article on this big discovery

says people with CFS can't handle stress. Did anyone consider that

perhaps it's not stress per se, but an excess of cortisol that pwc

can't handle? This kind of " discovery " is still worded to sound like

it's all in our heads (this gene predisposes us to be crazy) rather

than a physiological chain that creates undue stress on the body

resulting in fatigue. :-(

penny

>

> Kind of interesting:

>

> http://www.med.miami.edu/communications/som_news/index.asp?id=789

>

[Guest guest]

We've been discussing the CDC studies at cfs_research.

The study showing gene variants is not traditional in its methodology.

First there was no one gene that was of much significance in

separating cases from healthies. Instead the difference was in scores

produced by a formula that considered multiple genes (5, I believe).

I read it and I think(?) the methodology may well have been

theoretically sound (I'm no statistician). But the very influential

journal Science expressed discomfort with it, largely because I dont

think it is an approach that has yet been seen to yield consistent

results in practice. I suspect the finding will not be well-accepted

unless it is verified using a second cohort.

Personally I consider CDCs comments to the media that this is the

first biological finding in CFS, to be misleading and perhaps simply

incorrect. I also agree with an opinion that was voiced in Science:

that it is premature to be making conclusions about a stress-related

pathogenesis of CFS based on this genetic finding. What they did is

hypothesize that neurotransmission-related genes were involved,

examine only at those genes, find a statistically significant

correlation but one that hasnt been replicated, and then go to the

media using strong language. They didnt look at all of our other

32,950 genes (its too expensive to do so at this point in time) to see

if much more significant correlations might be found out there in

genes unrelated to stress response.

For a variety of reasons, I think Gows work is going to be more

informative than this work (assuming he has positive findings). I'm a

Gow fan ever since watching his pilot study presentation DVD. Solid

guy. I have some change left over from the DVD and want to know where

I can get my Gow Lab baseball hat and Dr Gow action figure. Hes

doing commonsense nuts and bolts stuff. I hope his effort, which was

previously in jeopardy, continues to be well funded.

>

> >

> > Kind of interesting:

> >

> > http://www.med.miami.edu/communications/som_news/index.asp?id=789

> >

>

[Guest guest]

Thanks much, .

Is there a website? I wonder why his work isn't discussed more at

the big CFS site?

penny

>

> We've been discussing the CDC studies at cfs_research.

>

> The study showing gene variants is not traditional in its

methodology.

> First there was no one gene that was of much significance in

> separating cases from healthies. Instead the difference was in

scores

> produced by a formula that considered multiple genes (5, I

believe).

>

> I read it and I think(?) the methodology may well have been

> theoretically sound (I'm no statistician). But the very

influential

> journal Science expressed discomfort with it, largely because I

dont

> think it is an approach that has yet been seen to yield consistent

> results in practice. I suspect the finding will not be well-

accepted

> unless it is verified using a second cohort.

>

> Personally I consider CDCs comments to the media that this is the

> first biological finding in CFS, to be misleading and perhaps

simply

> incorrect. I also agree with an opinion that was voiced in

Science:

> that it is premature to be making conclusions about a stress-

related

> pathogenesis of CFS based on this genetic finding. What they did

is

> hypothesize that neurotransmission-related genes were involved,

> examine only at those genes, find a statistically significant

> correlation but one that hasnt been replicated, and then go to the

> media using strong language. They didnt look at all of our other

> 32,950 genes (its too expensive to do so at this point in time) to

see

> if much more significant correlations might be found out there in

> genes unrelated to stress response.

>

> For a variety of reasons, I think Gows work is going to be more

> informative than this work (assuming he has positive findings).

I'm a

> Gow fan ever since watching his pilot study presentation DVD.

Solid

> guy. I have some change left over from the DVD and want to know

where

> I can get my Gow Lab baseball hat and Dr Gow action figure.

Hes

> doing commonsense nuts and bolts stuff. I hope his effort, which

was

> previously in jeopardy, continues to be well funded.

>

[Guest guest]

> Thanks much, .

>

> Is there a website? I wonder why his work isn't discussed more at

> the big CFS site?

>

> penny

>

I dont know, since I just went for the full texts (there were 5 or 7

of em published together in Pharmacogenomics). They are packed with

complex statistical analyses and I had to read each one about 3 times

with maximum effort to even understand it.

However, the critical editorial from Science was posted full-text a

couple weeks ago on cfs_research. Cort has also written some summaries

there.

[Guest guest]

Thanks for posting this, Penny. I would

assume this was based on an interview of Klimas, since it is out of the U. of Miami.

Okay, dumb question time. If the genes are

mutated does this mean the CDC will now look for infections that might have

caused those genes to mutate or will they assume that 900,000 folks in the US just

suddenly developed those mutations?

Any thoughts?

a

Carnes

Kind of interesting:

http://www.med.miami.edu/communications/som_news/index.asp?id=789

[Guest guest]

good question. Sounds like the study may not hold up well anyway. pennya Carnes <pj7@...> wrote: Thanks for posting this, Penny. I would assume this was based on an interview of Klimas, since it is out of the U. of Miami. Okay, dumb question time. If the genes are mutated does this mean the CDC will now look for infections that might have caused those genes to mutate or will they assume that 900,000 folks in the US just suddenly developed those mutations? Any thoughts? a Carnes Kind of interesting:http://www.med.miami.edu/communications/som_news/index.asp?id=789

[Guest guest]

> Okay, dumb question time. If the genes are mutated does this mean

the CDC

> will now look for infections that might have caused those genes to

mutate or

> will they assume that 900,000 folks in the US just suddenly

developed those

> mutations?

>

>

>

> Any thoughts?

a - thing is its not as dramatic as a mutation. Theres no unique

mutation like there is in cystic fibrosis or tay-sachs disease - not

at all. All it is, is just a slight difference in the distribution

of gene variants (alleles), all of which are also commonly found in

the normal population. You'd sort of shake your head if you saw the

data table. Say that for one gene there are two variants (alleles),

A and B. One can have two copies of A, two copies of B, or one copy

of A and B.

Well, the data are like this.

In their controls: 30% were AA, 40% were BB, and 30% were AB.

In CFS: 35% were AA, 30% were BB, and 35% were AB.

Thats a made up example (with numbers probably outside somethng

called Harvey-Weinberg equilibrium) but anyway thats basically what

this stuff looks like quantitatively. Didnt exactly take my breath

away when I saw these numbers. None of it is statistically

significant on a per-gene basis. The statistical significance only

occurs when they score 5 particular genes at once in a matrix. They

used exhaustive computation to locate this 5-gene set.

[Guest guest]

Thanks, got it. Well, it probably got

Klimas some income.

a

Carnes

> Okay, dumb question time. If the genes are mutated does this mean

the CDC

> will now look for infections that might have caused those genes to

mutate or

> will they assume that 900,000 folks in the US just suddenly

developed those

> mutations?

>

>

>

> Any thoughts?

a - thing is its not as dramatic as a mutation. Theres no unique

mutation like there is in cystic fibrosis or tay-sachs disease - not

at all. All it is, is just a slight difference in the distribution

of gene variants (alleles), all of which are also commonly found in

the normal population. You'd sort of shake your head if you saw the

data table. Say that for one gene there are two variants (alleles),

A and B. One can have two copies of A, two copies of B, or one copy

of A and B.

Well, the data are like this.

In their controls: 30% were AA, 40% were BB, and 30% were AB.

In CFS:

35% were AA, 30% were BB, and 35% were AB.

Thats a made up example (with numbers probably outside somethng

called Harvey-Weinberg equilibrium) but anyway thats basically what

this stuff looks like quantitatively. Didnt exactly take my breath

away when I saw these numbers. None of it is statistically

significant on a per-gene basis. The statistical significance only

occurs when they score 5 particular genes at once in a matrix. They

used exhaustive computation to locate this 5-gene set.

[Guest guest]

a, That is precisely what I was thinking. Are they

going to autimatically assume this is inhereted or are

thy going to consider that infection may have caused

the genetic components of the illness.

Marie

--- Penny Houle <pennyhoule@...> wrote:

> good question. Sounds like the study may not hold up

> well anyway.

>

> penny

>

> a Carnes <pj7@...> wrote:

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>

> Thanks for posting this, Penny. I would assume

> this was based on an interview of Klimas,

> since it is out of the U. of Miami.

>

> Okay, dumb question time. If the genes are mutated

> does this mean the CDC will now look for infections

> that might have caused those genes to mutate or will

> they assume that 900,000 folks in the US just

> suddenly developed those mutations?

>

> Any thoughts?

>

> a Carnes

>

>

> Kind of interesting:

>

>

http://www.med.miami.edu/communications/som_news/index.asp?id=789

>

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