Genetic Test Data Results = when do they become actionable?

[SunnyOne]

I've read the various comments on how genetic data can be used to assess risk of certain illnesses or adverse health conditions.

So you pull the data and then pay to have it interpreted... but then what do you do?

Your PCP presumably is not trained in genetic counseling or providing further guidance.

Also, let's say that blood tests have already revealed underlying conditions and now you have prescription meds
and have made lifestyle modifications.

What more can be done with the genetic data that makes it actionable?

Or does it exist to either give you some kind of peace of mind (if favorable) or potential night terrors (if negative).

I am being somewhat facetious here of course lol - just wondering how having this additional information
would be helpful in an actionable way?

Thank you.

 

[braumeister]

I am being somewhat facetious here of course lol - just wondering how having this additional information
would be helpful in an actionable way?

The way I look at is that the data from your genome may tell you something like "You are 15% more likely than others to develop [name of disease]."

With that information, you may decide to get whatever specific tests are available to look for signs of that disease.

That's really about all there is to it, AFAIK.

 

[Aerides]

I guess it depends on the test and result.

For example, a BRCA mutation carries a very high risk of breast cancer. Adding to that family history, you might want to take more aggressive steps to head that off, or at least get more frequent mammograms and other screenings than the general population.

 

[sengsational]

Peter Attia just did a long podcast on it. He was very suspicious of any "if (some genomic finding ) then this (thing they're selling, like diet, supplements, etc)". I'm not going to be able to summarize fairly because I've been biased against the idea, but I walked away after listening thinking "totally useless"

 

[athena53]

I also listened to Attia's podcast. (Yes, I know he's been discredited after it turned out he was sending raunchy and inappropriate e-mails to Jeffrey Epstein- no allegations whatever that he was on the island or involved with Epstein's victims. I figure I'm benefiting from his medical expertise, not dating him.)

"Actionable" is a key word: what are you going to do with the results? If there are just vague indications that you might be at risk for something but it's nothing under your control, is it worth testing? If tests show you're likely to develop Alzheimer's, will you start planning for your care now or just let that knowledge ruin the rest of your life? If the latter, maybe you shouldn't be tested.

Cancer- 95% of cancers are "somatogenic"- due to the aging process, smoking, environmental and other risk factors, etc. Only 5% are due to a genetic mutation. The BRCA mutations, an indication for breast cancer risk, are a notable exception and some women with a BRCA genetic mutation will get a preventative mastectomy. I have a niece on Tamoxifen- not because she has breast cancer but apparently it reduces your risk of getting it by 80%. Her mother, my sister, had a very small cancerous tumor they found on an MRI and she had a mastectomy 8 years ago. Sister tested negative for 33 different mutations. Our mother died of a recurrence of breast cancer at age 85 so I now alternate mammograms and MRIs every 6 months. Did not bother with genetic testing.

Results can also help family. When a first cousin heard about my sister's breast cancer she decided to have a lump checked out. It was cancerous and so far she's doing fine after treatment but it turned out that she had a genetic mutation that put her at risk. Her sister was tested. Sister had the mutation, too. It came from my Aunt's side and was also a risk factor in colon cancer, which killed her father- so their 3 brothers are on alert.

No concrete answers but I haven't found any reason to get genetic testing for anything.

 

[EastWest Gal]

I had a coworker that discovered she had the BRCA mutation. She chose a double mastectomy. I would have probably done the same. Two dear friends died of breast cancer in their 40s and 50s.

I had a coworker who chose a double mastectomy because she carried the BRCA gene.

Woody Guthrie had Huntington's chorea. Autosomal dominant, so that his son Arlo Guthrie had a 50/50 chance of the disease. Would have it eased his mind to know he did not have the disease? Maybe. But at age 78, he need not fear that awful illness, as it would have already shown up.

My parents' next door neighbor, the older brother of one of my childhood classmates, lost an infant to Niemann-Pick disease, a rare genetic disease that resulted in a slow, painful death of their infant. Fortunately prenatal testing had been developed and they were able to have a healthy child afterward, without the fear and uncertainty.

In the 1970s, one of the major medical breakthroughs was the ability to prenatally test for Tay Sachs disease, a rare, 100% fatal genetic disease that was horrific on families, as it caused pain and seizures to infants before they succumbed within a year of their birth. That, coupled with the Roe v.Wade decision, allowed couples who would never had a child with a 25% chance of the horrific illness, to bear completely healthy children. That was a win.

There are salient, very specific reasons to get genetic testing. Before you do, ask yourself what it would change? For the former coworker, she removed her breasts. For two friends who did not test, they lost their lives.

Delve into one's family history first. Other than smoking related illness, which is not something that affects me, other than my childhood exposure, the women on both sides of my family lived long and happy lives into their 90s. A few broke 100, including the men.

Tne question remains: how will such knowledge change you? You can answer that question yourself, and that answer can always change, depending on your circumstances.

 

[athena53]

Woody Guthrie had Huntington's chorea. Autosomal dominant, so that his son Arlo Guthrie had a 50/50 chance of the disease. Would have it eased his mind to know he did not have the disease? Maybe. But at age 78, he need not fear that awful illness, as it would have already shown up.

Genetic testing can also show if you're a carrier. Before this was an option, some people chose not to have children because they didn't want to pass on a genetic condition. Arlo had 4; don't know about their health status. Definitely useful in deciding whether or not to have children.

 

[Act2]

A gentleman I know had bile duct cancer; then he was tested for the BRCA2 genetic mutation that is linked to breast cancer, as this mutation is not just a contributing factor for breast cancer but also for pancreatic and other hepatobilliary cancers such as the bile duct cancer. Turns out he did inherit the BRCA2 mutation (from one parent, so he has an increased risk but not as high as if he inherited it from both parents) and he is now on an annual mammogram schedule as part of his post-cancer follow up. There isn’t any way that he or any man would know he’s at increased risk for breast cancer without the genetic testing, and now his relatives are also being tested, male and female.

 

[Lorenzo]

So you pull the data and then pay to have it interpreted... but then what do you do?

That's exactly what my PCP asked me in a sort of rhetorical manner when I asked about it. As noted by others above, there are some mutations for which a preventative procedure may be reasonable. My wife tested for one that might have run in her family--and tested negative. For me, there would really have been nothing I could do that would have made a difference.

 

[Koolau]

I'm sure there are exceptions, but as pointed out in several posts, genetic testing seems to lead to more questions than answers. I'm not suggesting "not" to test, but I think the questions should be asked before hand (IOW "what would you do IF the test said 'XYZ'")? These are not trivial issues and deserve a lot of up-front thought before action IMHO.

 

[athena53]

When my brother was running our elderly father around to way too many appointments with specialists he had three questions when they wanted to order yet another test: What are you looking for? What are you trying to rule out? What will you do in response to the results? If he didn’t get a solid plan on #3 the test didn’t happen. I think those questions apply here, too.

 

[Koolau]

When my brother was running our elderly father around to way too many appointments with specialists he had three questions when they wanted to order yet another test: What are you looking for? What are you trying to rule out? What will you do in response to the results? If he didn’t get a solid plan on #3 the test didn’t happen. I think those questions apply here, too.

My PCP tries to ask those questions before ordering tests. For instance, together PCP and I agreed no further PSA tests.

 

[kirby]

I did this and made lifestyle changes, it also confirmed several aspects of my life/health that I could never fix forcibly/confirmed suspicions.

I ordered a genome sequence directly through a vendor, they are realitvely inexpensive abroad, but it's a complete test, something like ancestry or 23andme do not provide a full genome mapping/sequencing.

Sequencing.com, Nebula, and other vendors offer a full flat file after they sequence your genes. Yes they are expensive in the USA.

Then there are a few additonal tools, like promethease which takes your genome file and spits out a ranking of what genes you have that are linked to diseases.

You can also run it a bit offline on your computer using something like GitHub - Ensembl/ensembl-vep: The Ensembl Variant Effect Predictor predicts the functional effects of genomic variants or Ensembl. This helps to run it against ClinVar - Home

It will dump out a spreadsheet be searchable for what traits you have, positive/negative. Usually by a gene ID, liklihood, if it's good or bad and what it is.

For me, it helped identify/confirm some aspects of my ancestry based on genes that are specific in certain areas of the world and recessive/dominant genes for hair color, eye color, skin color. It was really cool, confirmed that via paper trail.

The other traits like blood type, gender, heart disease, diabetes and other genetic diseases etc also give more insight. So you can confirm. I did this a few times with blood tests and then used other blogs and researched more about heart disease, like what was posted on myticker.com - e.g. *if* heart disease is present, genetic testing/blood testing only happens more as you get older but if you take advocating yourself and do the tests you can get good insight from the beginning and address it early on - for heart disease that usually even means starting a statin early, but talk to your doctor first.

This a good example of someone blogging about what they did and they used some of the tools I did: https://joemcgirr.github.io/files/code_tutorials/my_genome/SnpEFF.html It's almost what I did exactly. I also invoked AI tools to review and extrapolate other genes, which some people don't like, but you can run a local LLM to help and bounce around as well as anonymoize the dataset within excel good enough.

It's a very popular conversation in certain online circles, happy to see it here too, it was a very effective early warning system for me to fix some key functions and being in my 30's, I was able to correct them immediately and have answers for why my body is a certain way.

 

[Alan]

My mother died of a rare type of cancer in 1995 and myself and 3 siblings did testing for the gene mutation that increases the probability of developing it. One of my 2 sisters has the mutation so she has annual screening in case she develops the cancer in order to catch it early.

 

[Montecfo]

It seems a very mixed bag to me. Genetically linked disease may not express itself due to other genetics. And the link itself may not be well understood.

Caution in order I think.

 

[Koolau]

I guess I'm wondering at what age you decide to forgo such testing. I'm pushing 80 and kinda figure I've already lived a pretty long life. I already have heart disease and have had cancer. I'm worried about Alzheimer's but don't think "knowing" I'm at higher risk would change much in my behavior or diet, etc.

Just thinking out loud here. There must be some age when the testing would be a waste of time and money.

 

[target2019]

Consumer genetic tests are not actionable. Gene panels are ordered by MD and interpreted by genetic testing companies.

It's a fascinating subject for sure.

 

[Koolau]

Consumer genetic tests are not actionable. Gene panels are ordered by MD and interpreted by genetic testing companies.

It's a fascinating subject for sure.

Sorry. What does "actionable" mean? Thanks.

 

[skyking1]

I guess I'm wondering at what age you decide to forgo such testing. I'm pushing 80 and kinda figure I've already lived a pretty long life. I already have heart disease and have had cancer. I'm worried about Alzheimer's but don't think "knowing" I'm at higher risk would change much in my behavior or diet, etc.

Just thinking out loud here. There must be some age when the testing would be a waste of time and money.

I have a colonoscopy scheduled this summer, the first follow up after no issues. I know at some point I will not have another. Same thing goes for PSA.

 

[target2019]

Actionable is used in the thread title. Others are using it differently than I. In this case of genetic science I would say it means medical action or course.

Various gene panels which were based on biopsy kicked off my treatment.

 

[kirby]

estments would have been made already had it not been for some pretty stunning value propositions and ROI already realized

Consumer genetic tests are not actionable. Gene panels are ordered by MD and interpreted by genetic testing companies.

It's a fascinating subject for sure.

Actionable is used in the thread title. Others are using it differently than I. In this case of genetic science I would say it means medical action or course.

Various gene panels which were based on biopsy kicked off my treatment.

I disagree. A cheap 99$ test from 23andme or a complete genome sequencing? Both give actionable information depending you know what they are for and how to use them.

A proper Genome Sequence is not cheap, in China you can do it for sub $300, in the USA it's about $500~

Genome Sequencing Costs and DNA Sequencing Costs: Data


And decreasing rapdily, so it's not to expensive considering it can help spot potential risk. It's the same as doing your own MRI or your own blood tests. it's a new paradigm (lol that phrase) meaning that if you choose the right consumer available test, bypassing your physician, and take a deep dive you can see what your genome has in store for you.

For example I would've never asked for a few genetic/blood tests that were positve in my genome to confirm I had a condition. While it has not manifested yet, knowing that I currently have it was "wow" and having that future foresight is invaluable to get it under control so it never becomes an issue.

There would've been no order by an MD because I had no symptoms and had no family history of it. I would've had to had a severe reaction, spend time back and forth with an MD or two and a specialist to identify it.

But because I did a genome sequenced, promthease picked it up as high risk, I also ran a few AI tests in an agentic workflow to verify it and got the subsequent RS and Gene and verified it by ordering my own tests - It's easier in Asia, it's essentially self service conceirge and blood tests/genome testing for exact genes cost sub $10 in some regions - meaning Genome, paid sub $300, then individual blood tests and individual genome testing to verify everything.

And boom, two emperical sources verifying information independent of one another.

For example, this is a innocent one but it does explain alot for me:

Metabolism

Caffeine sensitivity (ADORA2A; anxiety/jitters)

ADORA2A

rs5751876

T

TC

1​

See implication text; confirm strand/orientation for medical decisions.

0: Lower sensitivity | 1: Intermediate | 2T: Higher sensitivity (mixed evidence)

0​

Possible

1​

0​

Yes (direct)

See implication text; confirm strand/orientation for medical decisions.

Promothease generates it in a spreadsheet, identifies the trait, then the gene: ADORA2A, identifies the RsID: rs5751876 has a T for the affected allele, and shows what is in my genotype, TC.

If I wanted more info, I can google/scholar.google.com the gene and the RsID or hop onto snpedia for possible combonations, etc: rs5751876 - SNPedia

This example is highly studied, has high correleation and has high signal for other genes. Alot of risky genes are studied because they are easy for studies to be approved, emperical data is easy to collect and it really becomes a test to look for this gene at this location with the allele there.

For example there are some solid studies and proof about medicial interactions, if you have this gene w/ this allele then you are most likely affected by x for example


Goes for alot of things, the easy ones are eye color, hair type, skin color, phenotype identifiers.

Then theres some good reseach on like the idea of fat/obesity.

FTO/ rs9939609

Is the primarily identified gene for body obesity. If you have this, it is very hard to lose weight, diet/calorie intake be damned: Checking your browser - reCAPTCHA

Once you have your genome you can really drill down what affects your body and what your future could've looked like if unmonitored.

tl;dr If you're under 60, it is beneficial, it will tell you high potentially what you are at risk for and many things are preventable, and soon with CRISPR it may even be able to be turned off. I specifically did not want to list cancers, and other genetic disease, but there is high correleation if you have a certain allele per gene it is a prediction marker for those scary diseases.

 

[UpQuark]

My brother's DNA results said he has both of some gene that causes hemachromatosis (too much iron builds up and damages organs). His doctor said the problem is usually found on the autopsy table. So he's getting treatment (blood removed, not sure if anything else).
When my brother sent me the info I checked my DNA results and I got lucky on both copies of the gene.

 

[sengsational]

A person might discover a BRCA or Lynch syndrome mutation despite an apparently unremarkable family history, so that's a thing. And there's some heart risk genes that might get discovered. The sum total of those is about 1 in 100, but if you are the one, well, it was worth it! And you're on your way to treatment before the crisis!

The other 99 people, meh. You probably already know it (if you go to the doctor and have a decent family history), or you won't do anything different knowing it.

As for quitting the PSA, sure, if you know you're on your way out soon via some other route, don't bother. But the population level "don't screen" logic doesn't hold at the individual level. If you are otherwise healthy and aren't running out of runway, watching PSA velocity seems like a no brainer. Mine was up, and both me and my PCP just yawned. The next one was down. It's how you react that can get you into trouble. Again Peter Attia did an episode on this and times and technology has changed; the old thinking has been updated.

 

[Montecfo]

Yes I do not understand passing on the PSA test in general.

 

[Dash man]

DW had ovarian cancer 22 years ago. Thank God she beat it and is still will us. Her cousin did not survive. She was advised by her doctor to test for the BRCA gene, since many ovarian cancer patients also carry it. She had decided before the test that if it were positive, that she would have a double mastectomy. Fortunately, she did not have it.