why do a whole genome sequencing?

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..

 

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.

 

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.

 

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.