New study finds vast majority of diseases have only a very small genetic contribution of 5% to 10% at most (so much for 23andme testing)

[Wishful]

My guess is that the gut microbiome research will go the way of the human genome project:

I feel the same. I expect that a small percentage of the population will get effective treatments for a gut microbiome based problem, but the main beneficiaries will be companies selling *Wonder Treatments* (ineffective) flogged by health magazines.

I doubt that microbes will prove to the *the answer* to most diseases either. It will probably turn out to be just one more factor among many, and that diseases will be the result of combinations of many factors, with no easy answers for how to predict or avoid or treat diseases.

Instead of trying to fix our complicated evolved bodies, the human race would probably be better off engineering a superior race, whether organic or electronic. Of course, being flawed humans, that project probably wouldn't turn out well...

 

[Hip]

Instead of trying to fix our complicated evolved bodies, the human race would probably be better off engineering a superior race, whether organic or electronic.

Like all of us here, having experienced the miseries of long-term chronic disease, if there is such thing as reincarnation, the next time I come back to Earth, I want to be a shiny robot with consciousness. That way, if anything goes wrong with my body, I'll just need to buy a replacement part!

 

[Rufous McKinney]

So we need to start looking at these environmental factors to explain disease, environmental factors like chronic pathogenic infections and toxic exposures.

I"m still confused- if the concordance rate for ME CFS is this reported 55%; that suggests there IS a genetic predisposition....in this case.

 

[Hip]

I"m still confused- if the concordance rate for ME CFS is this reported 55%; that suggests there IS a genetic predisposition....in this case.

I don't understand all the ins and outs of it, but I've read that concordance rates as a means of determining the genetic component of disease is not a reliable quantitative measure, because you cannot fully separate the genetic effects from the environmental effects. For example, most twins will grow up in the same home, and so share the same environment, at least when they are younger. So any toxin or virus going around in the family environment may affect both twins.

If the disease concordance rate is much higher in identical twins than it is in fraternal twins, that suggests there are some genetic causal factors which contribute to the development of the disease.

So from the concordance rate data we can say ME/CFS involves some genetic contributions to disease development, ie, it has some heritability, but it's hard to say how much.


Genome-wide association studies (GWA or GWAS) like Wishart's offer another approach to measuring heritability. In Wishart's study, he seems to have quantified heritability. Just how accurate his heritability figures are, I could not say, as I know very little about GWAS techniques.

 

[Rufous McKinney]

because you cannot fully separate the genetic effects from the environmental effects.

That makes some sense, as even twins raised in separate environments, for instance, are likely to have experienced considerable shared environmental exposures. Exposure to, say, really common pesticides like glyphosate or malathione.... Ground asbestos emanating from the roadways...all that. Amalgam fililngs/metals.

Unless you could really find a twin raised in, say a remote igloo. ANd they never saw a dentist.

The twins are likely vaccinated.

(pondering why my older brother didn't have these types of illnesses, and I did)...he was 16, when I was 10. I got mono at 10. I'm living in sprayed orchards and I rode a bicycle from the time I was 10 until I was 20, riding a bicycle thru and around these sprayed orchards in rural Nor Cal.

My brother is driving a car to school and I'm riding a bike. THe exposure to toxins I recieved was likely much higher than his exposure. We also recreated in orchards, hiked through them, hung out in them. My brother hung out in the living room.

So I have potential high exposure to pesticides during four rounds of Eppstein Barr. If I need a Why, this works for me.

 

[Learner1]

Let's just agree that both genes and environmental factors cause many diseases.

ME/CFS seems to be a collection of common symptoms caused by a variety of problematic genetic and environmental factors.

 

[Hip]

Let's just agree that both genes and environmental factors cause many diseases.

Have you read Prof Paul Ewald's take on genetic causes of disease? Ewald says:

Ewald disagrees with the popular theory that genes alone dictate chronic disease susceptibility. Ewald, whose background is in evolutionary biology, points out that any disease causing gene that reduces survival and reproduction would normally eliminate itself over a number of generations.

Ewald says that "chronic diseases, if they are common and damaging, must be powerful eliminators of any genetic instruction that may cause them."

One example of this is schizophrenia; patients with this mental illness rarely reproduce. Ewald argues that, just by evolutionary pressures, schizophrenia would have already been eliminated if its causes were strictly genetic; he suggests that in the future, an infectious cause of schizophrenia will be discovered.

Ewald explains that purely genetic causes of chronic disease will persist only if a genetic instruction provides a compensating benefit (for example, the disease sickle cell anemia is caused by a genetic mutation that, in heterozygotes, protects against malaria, which kills millions worldwide each year).

 

[Rufous McKinney]

Have you read Prof Paul Ewald's take on genetic causes of disease? Ewald says:

An illness like ME does not necessarily reduce survival and reproductive output. Many people with ME have successfully reproduced. This illness did directly influence (reduce) the number of offspring I was able to produce.

There could be some adaptive benefits to some form of our version of a more sensitive immune system- if that in fact is a central theme in the ME saga. Perhaps some of those sensitivies were adaptive, in the world we evolved in which did not have so many toxins (unless you were munching on plant alkaloids).

 

[Hip]

An illness like ME does not necessarily reduce survival and reproductive output.

I bet ME/CFS would reduce survival in times when life was a lot harder, when everyone had to toll on the land in order to grow food to survive.

 

[Learner1]

@Hip Unfortunately, people with mitochondrial diseases, celiac, hemochromatosis, Huntington's, and many other genetic diseases reproduce just fine.

And, yes, we are agreed that environmental factors have a great impact on type 2 diabetes, autoimmune disease, and obesity.

And, some cancers have genetic drivers while others are more driven by environmental factors.

 

[Hip]

@Hip Unfortunately, people with mitochondrial diseases, celiac, hemochromatosis, Huntington's, and many other genetic diseases reproduce just fine.

According to Ewald, the genes that cause these genetic diseases will have only propagated down the generations because they provided some compensating evolutionary survival advantage.

For example, this paper posits that the hemochromatosis genes which cause excess iron retention may have appeared when European Neolithic humans migrated northwards into colder climates, because these genes allowed for better thermoregulation in the cold.

 

[JES]

An illness like ME does not necessarily reduce survival and reproductive output. Many people with ME have successfully reproduced.

In today's society yes, but in the surroundings where most of our evolution happened, living in caves, where survival very much depended on your physique and finding food every day was a challenge, I wonder how many would really successfully reproduce with ME/CFS (which is all that matters, the modern history is pretty much irrelevant in evolutionary time scale). Having a minor disease, if it meanwhile compensated by providing some other advantage, maybe it could live on, but something as physically detrimental as ME/CFS and with a large prevalence of around 0.5%, I find it hard to believe evolution wouldn't have picked it out if it was mainly genetic, so I think the point Ewald is making is relevant here.

There is a counter to this argument and that is if you are getting ME/CFS after reproductive age, then evolution pretty much doesn't care what happens, but the data seems to suggest that ME/CFS has onset peaks at ages around 15 and 35.

 

[Hipsman]

There has also been Fivefold to eightfold increase in the incidence of ME from 1980 to 1989

This would suggest that something in environmental factors triggered this increase. If we take ME/CFS cases after this 5 to 8 fold increase in ME as 100% (this is all of diagnosed cases), then out of this 100% at least 80% to 87.5% come from this new environmental factors.

I think this would suggest that there is a genetic predisposition, but "it" was only activated after this new environmental factors kicked in, maybe it was polio vaccine... This seems like epigentics to me.

 

[IThinkImTurningJapanese]

I bet ME/CFS would reduce survival in times when life was a lot harder, when everyone had to toll on the land in order to grow food to survive.

Growing food is easy. Foraging is easy. Hunting is relatively easy.

Supportive social structures can be difficult though.

 

[Wishful]

There has also been Fivefold to eightfold increase in the incidence of ME from 1980 to 1989

I think the reliability of that figure is poor, since we didn't have any way to properly diagnose ME then, and still don't. Many reported cases might not be ME, and there's no real way to know how many unreported cases there are.

I wonder if there are any medical historians who can find out whether there were cases (or epidemics) of ME at different times in the past. It would be really interesting if there was nothing clearly matching ME until something like DDT was in widespread use.

 

[Hip]

I think the reliability of that figure is poor, since we didn't have any way to properly diagnose ME then, and still don't.

I think it's reasonably reliable, because as well as other sources, it is based on UNUM insurance's own claims data. UNUM reported that claims for disability due to ME/CFS had increased by an enormous 500% in the four years from 1989 to 1993.

This massive increase in ME/CFS in the 1980s was in fact the reason dubious insurance companies like UNUM teamed up with the Wessely School psychiatrists in an attempt to recast ME/CFS as an "all in the mind" psychogenic condition, so that UNUM would not have to pay disability support to patients (because insurance rules stipulated no pay outs for long-term psychological conditions).

Had it not been for the huge increase in ME/CFS cases in the 1980s, we would never have had these disability insurance company shenanigans, that caused so much harm and damage to ME/CFS patients and ME/CFS research.

 

[Hipsman]

I think the reliability of that figure is poor, since we didn't have any way to properly diagnose ME then, and still don't. Many reported cases might not be ME, and there's no real way to know how many unreported cases there are.

I would think that since nothing changed in regards to diagnostics prior and during this Fivefold to eightfold increase, the likely hood of someone being diagnosed or misdiagnosed was the same. The chance of someone being misdiagnoed would probably be less in 1989 then in 1980 due to better tests for other diseases.

 

[Wishful]

What I'm wondering about is the difference between 'incidence of ME' and 'reported cases of ME'. It took me about 15? years to figure out that I had ME, and before that I thought I had some sort of very rare chronic neuroimmune disorder. The increase in reported incidence might just be due to an increase in awareness of ME, or in the case of insurance claims, and increase in the numbers of doctors willing to diagnose it as ME. The lack of a clinical test for ME makes it hard to know the true rate of incidence.

I think the rate of incidence has increased, but the lack of a way to prove it makes the true numbers hard to determine.

 

[Hip]

The increase in reported incidence might just be due to an increase in awareness of ME, or in the case of insurance claims, and increase in the numbers of doctors willing to diagnose it as ME.

That's one way to interpret it, but why should there be an increase in awareness of ME/CFS only, and not other diseases? If the general public was becoming more savvy in their medical understanding of disease, then you might expect this to be for all diseases, including multiple sclerosis, Parkinson's, etc. But we don't see large increases in these diseases in the 1980s.

 

[Hipsman]

The increase in reported incidence might just be due to an increase in awareness of ME, or in the case of insurance claims, and increase in the numbers of doctors willing to diagnose it as ME.

Fivefold to eightfold increase in diagnostics due to better awareness? I mean, with no internet someone was very unlikely to hear about ME/CFS from anywhere except their doctor, the doctors or GP's to this day only have one paragraph about ME/CFS in university textbooks, most likely Dr's back then would not know how to diagnose ME/CFS unless they learnt about it themselves. And we know that even now very few Dr's are willing to do that.

After the added "all in mind" stigma to ME/CFS that happened sometime during 1980-1989 there was probably even less insentive for Dr's to diagnose patients...