Options for genetic testing

[Yessica]

I have a 23 and Me kit in my room for years. Hesitant to use it cause of privacy issues.

Was wondering are there tests that a doctor's office can run that would be similar to 23 and Me? Then I wouldn't have to be concerned about my results, how they are going to use it now or in the future with decisions made regarding them at 23 and ME or other companies.

I think I have issues with Vitamin B. From what I've researched it may be playing a role in some of the things going on with me.

I've had the 2 blood tests the doctors do for it. I'd like to have something more comprehensive that may show why I'm having problems with Vitamin B and anything else that may be up.

Over the years I've read bits and pieces on threads at the other place on B12, SNPs, etc. I need to understand it better yet would like to have more thorough genetic testing to work with as I proceed.

Were any of your doctor's office able to do this kind of testing or does it have to come through companies like 23 and Me? Or is there another option that still would give us confidentiality with our medical information? Thank you for any help with this.

 

[MarcNotMark]

Or is there another option that still would give us confidentiality with our medical information?

According to this article:
https://torontophysiotherapy.ca/genetic-privacy-anonymous-23andme-results/
It would be possible to do the 23andme relatively anonymously, although not bullet proof.

.......... but

I have a 23 and Me kit in my room for years.

If you had the kit send to your home address it may already be too late for that

ETA: or order a second kit in the way described in the article.

 

[Kitty]

Before you decide, it might be worth asking whether this kind of testing will tell you anything reliable about your ability to absorb or utilise B vitamins.

Having a particular variant may not determine how your body works, as genetic traits often have highly variable penetrance, and there may be other factors that balance out any potentially deleterious effects.

I have to inject vitamin B12, for instance, but not because of my genetic heritage. It's the result of a common bacterial stomach infection that was left untreated for too long.

I guess I'm trying to say (in a long-winded way – sorry!) that there's huge amount of stuff written about these topics on the internet, and some of it is generated by people with no training in medicine or genetics, who're marketing supplements or 'therapies'. Caveat emptor and all that.

 

[Jonathan Edwards]

I agree with @Kitty. If the ordinary blood test do not show anything, genetic testing will tell you nothing. Genetic tests might tell you why your blood tests are abnormal, if they are, but if they are normal then the genetics will be irrelevant. Genes can only have an effect through the chemistry that ordinary diagnostic tests assess.

 

[Hoopoe]

Effectiveness of clinical exome sequencing in adult patients with difficult-to-diagnose neurological disorders

My summary: hereditary neurological diseases are difficult to diagnose. The study assessed the usefulness of whole exome sequencing as first-line diagnostic tool in adults. 27% of patients had a known or suspected pathogenic mutation. Patients with illness onset before the age of 40 were more likely to have a genetic cause of illness. This approach was cost-effective and shortened the diagnostic odyssey of a third of patients.

https://onlinelibrary.wiley.com/doi/full/10.1111/ane.13522

My thoughts: this seems relevant to ME/CFS as well. A portion of patients currently diagnosed with ME/CFS will be misdiagnosed and in reality have a difficult to diagnose genetic disease. These diseases can be present with numerous and heterogeneous symptoms, with atypical symptoms, may not be noticable until later in life, may have an apparent trigger. If this approach is cost effective and shortens the time for a diagnosis then it could be widely used and would improve the lives of patients.

How many ME/CFS patients would benefit from whole exome sequencing?

 

[Mithriel]

A very good idea and it could even show a pattern within the ME group.

Before PCR, it happened that microbiologists knew something was there even if they did not know what it was.

Hepatis C was like that. Something called non A/ non B was known for years before they managed to find out what it was.

 

[voner]

I’m currently pondering whether to do a whole genome sequence test or not and I am hoping to solicit some educated comments.

here’s the situation. I live in the USA and my health insurance is Medicare which is the government backed insurance system. My consulting MD is a neurologist at an University related teaching hospital and who keeps up with his field closely (especially genetics) and is a good communicator. For the last year and a half my doc has been ordering genetic testing from this company, Invitae (https://www.invitae.com/en), which has genetic panels you can order free of charge to me under the Medicare system. We have run many panels; neuromuscular, immunological, mitochondrial and some for specific diseases. none of these have popped up anything significant.

so at my last consult I had I asked my doc why we don’t just run a whole genome panel and he said that was something to consider at this point. The issue is that Medicare will not currently pay for a whole genome sequence, so I have to self pay. He uses the company Variantyx ( https://variantyx.com ) because they have the least expensive testing regime. I have been told the cost will be $1000 for the test and report.

Invitae updates and adds to their panels frequently and has excellent customer service in my experience, so we can rerun these panels every year for no cost to me.

I really have not been able to find much information about the benefits of doing a whole genome sequence at this point. I had a consult with a geneticist who works with my doc, but it really was no help.

So, any opinions on the current state of the art whole genome sequencing being beneficial in the clinic setting?


right now I am leaning towards delaying the WGS indefinitely..

 

[Creekside]

How likely is it that the testing will lead to a useful treatment or warn you of a serious potential problem that you could avoid? I vaguely recall reading of a few cases where such testing has led to a treatment for some rare disease, or warned of something avoidable, but how many 'worthwhile' results vs how many total people testing? The marketing of this testing obviously wants to exaggerate the benefits.

Also, what downsides are possible? Learning of a high likelihood for a disease that you can't do anything to avoid? Being turned down for insurance or jobs because of a certain marker? I'm not sure whether the latter is fact or fiction, but it certainly sounds possible.

I think it's mostly a profitable gimmick.

 

[Hoopoe]

I don't have anything particularly insightful to contribute. Having done whole exome sequencing, whole genome sequencing would be a possible next step for me but it seems hard to justify when there are so many unknowns and I have little income.

In the literature, "diagnostic yield" seems to be the technical term for being able to make a diagnosis based on the results of genetic sequencing. You could try searching for diagnostic yields for whatever categories best descirbes your illness.

For example, searching for "diagnostic yield neurological disorder" finds relevant studies.

My impression is that whole genome sequencing generally slightly improves the diagnostic yield compared to whole exome sequencing, but that is usually for patients where there is a suspicion that genetics is relevant in their case.

Being able to tell when an illness is likely genetic is a very useful skill to have.

 

[Kitty]

I think it's mostly a profitable gimmick.

I tend to agree. I don't think genetic diseases are often found accidentally through WGS; they're found, sometimes after many years, by the right expert recognising the symptoms, and then confirming it through genetic tests. Or at least trying to; in many cases not all the variants concerned are even known. The VUS (variant of unknown significance) list is often fairly long because it can be difficult to establish whether or not a particular change causes enough enrichment to result in disease. A lot of evidence has to be gathered and studied, which is expensive.

You might possibly get lucky with a WGS, but I suspect most people learn little or nothing meaningful from them. I've read a lot of guff in discussions about genome sequencing, with people claiming to have this or that variant that affects the processing of some vitamin, mineral or protein, but when you look into it, it's clear that it doesn't necessarily have any consequences at all in real life. There are far too many variables at play.

 

[Kiristar]

I'm seeing increasing research into the genetics of ME like the recent precision analytics paper. So a general question. Has anyone sequenced their own DNA and used it successfully to identify potential causes or problems and then relevant possible treatments that help symptoms eg diet changes, supplements, addressing deficiencies etc?
If so which sequencing company did you use (I don't want my data sold eg by 23&Me) and which analysis company did you use to get actionable, comprehensible insight.
I'm in the UK and top end severe.
I came across Dante Labs (an Italian US company) and wondered if it's of any use but it's pricey.
Tia...

 

[Kitty]

Apart from genetic haemochromatosis, I can't remember people saying they found useful, reliable information via direct-to-consumer tests.

We don't know enough about ME genetics to pinpoint potential risk factors until DecodeME is completed, so a report won't uncover anything about that. I'd be fairly surprised if an analysis done by one of these companies pointed out many other genetic conditions, as so many of them seem to require detailed, expert sequencing of very specific regions of DNA rather than a general whole genome analysis.

I think it might be a waste of money and energy, to be honest, as it couldn't tell you whether you're deficient in something, suggest supplements to take, or highlight whether dietary changes might help. These companies sell people the idea of unlocking the secrets of their DNA without mentioning that genetics is too complicated, and we know too little about it, to do anything of the sort.

 

[RedFox]

We don't know enough about ME genetics to pinpoint potential risk factors until DecodeME is completed, so a report won't uncover anything about that.

And even if we knew the risk factors, they wouldn't mean much to someone who already has ME. Though I'm sure some people will enjoy finding out what genes the have for curiosity's sake.

 

[Hoopoe]

I'm seeing increasing research into the genetics of ME like the recent precision analytics paper. So a general question. Has anyone sequenced their own DNA and used it successfully to identify potential causes or problems and then relevant possible treatments that help symptoms eg diet changes, supplements, addressing deficiencies etc?

I had my genome sequenced and am still in the process of trying to interpret the resulting mass of information. It's possible that actionable information will come out but obtaining it is hard work.

A typical person has between 4 and 5 million variants in their genome. The effect of most of these will be unknown. Rarely, it will be a variant where the effect is known reliably. Sometimes an educated guess be made. Some of the information in genetics databases is also outdated or wrong. Many of the variants will have characteristics that makes them potentially disease causing and relevant to the person's illness and it will require a lot of work to identify the ones that matter. In some cases to confirm the pathogenicity of a mutation you'll need transgenic animal models.

If there is a suspicion of a genetic cause of your illness, then I think your best bet is to consult a clinical geneticist.

23andME is not very useful.

 

[Jonathan Edwards]

I heard a useful bit of information from our local genetic screening unit for rare metabolic diseases. These people diagnose things like Fabry's disease, mitochondrial myopathies, and Morquio syndrome. They have increasing numbers of referrals of people who have had 23andMe or other commercial sequencing done. In now over 300 such cases NOT A SINGLE USEFUL RESULT WAS FOUND.

 

[janice]

As far as I know the DEcode ME study is the first , biggest and imo the current best chance of getting some useful information.

My understanding tells me that although the DNA information can be seen as the foundations to personal immune responss to disease, allergens, stress, biochemical networks and pathways, due to life, Epigenetics, pollution, ageing, randomness, etc, etc each persons response to anything and everything is highly individualistic.

Therefore I feel it’s the downstream consequences of all of this muddle that is the useful data, ie how pwME respond to movement challenges/ energy using challenges perhaps. Or how our HR deal with daily living tasks, how these responses change depending on the level of poisoning/illness we are in whilst trying these things?

I feel the most useful data comes from longitudinal studies where the patients are clearly diagnosed and defined. Unfortunately for all sorts of reasons there have been precious few of these.

I am hoping that with the huge upsurge in LC and then ME that this will create sufficient awareness of the devastation to sufferers and their families lives, that something will improve and so help us all.

 

[MeSci]

I'm pretty sure that all transgenic animal models will do is cause animal suffering. They will not confirm or identify human effects.

 

[Hoopoe]

I'm pretty sure that all transgenic animal models will do is cause animal suffering. They will not confirm or identify human effects.

Your intuition is not correct. Animal models of specific genetic defects can confirm the relationship between the mutation and the disease observed in humans. I've read many papers where such findings were described.

I share your concern over the well being of animals. Animal here can just mean a fruit fly. Yeast models can also be used.

 

[MeSci]

Your intuition is not correct. Animal models of specific genetic defects can confirm the relationship between the mutation and the disease observed in humans. I've read many papers where such findings were described.

I share your concern over the well being of animals. Animal here can just mean a fruit fly. Yeast models can also be used.

It's a lot more than concern. I gained a Masters degree in science, and focused particularly on the reliability, or rather lack of it, of animal studies.

An awful lot of science papers are rubbish.

Yeast isn't an animal, as I expect you know.

 

[Yan]

I got my whole genome sequenced 2 years ago. Haven't found many good leads that would explain my illness yet though. But there's this one mutation in TSFM (Ts translation elongation factor, mitochondrial) gene that's marked as pathogenic in ClinVar that I've been pondering about. It's quite rare globally except in Finnish population that I'm part of. It's enriched here as 1:80. It's associated with "Combined oxidative phosphorylation deficiency 3" and "Primary dilated cardiomyopathy". It could be relevant because my mother died at age 25 from cardiac arrest. But echocardiogram didn't show any abnormalities in my heart. According to literature "no homozygotes were identified or reported, suggesting that homozygosity may be lethal" and so mine is heterozygous too (phew).

The reason I've not yet tried to get it examined by medical professionals is that it's after all quite common in Finland and I'd think there'd be some more talk here about it if it caused disease/symptoms in everyone who has it. And I actually mentioned it to my doctor but was quickly brushed off by "genetic testing is expensive and takes a lot of time" argument.

Anyways, I too am looking forward for the results from the DecodeME and hopefully something useful will be found trough it!