> For several years, 23andMe has worked on demonstrating that its reports are easy to understand and analytically valid...
I guess these are different reports, but I know a genetic counsellor who describes 23andMe's carrier screening tests as "the bane of their existence". Those reports seem not-so-easy to understand based on the patients she sees.
One problem is that they warn that your offspring are at high risk for some condition, when really "high risk" means 0.5% higher risk than the general population. The other is that they may say you are not a carrier for a certain condition, when they only test for one variant of it, where proper tests will test for multiple variants. They can both scare and soothe irresponsibly.
When I signed up the sample they took was spit in a vial.
It never clicked for me that this was going to be the most scientifically accurate reading of my health in all the world. I took part because it could give me some scaring and soothing. But I assumed I'd go get a real test done if I was actually worried or interested about something specifically.
The website repeats this sentiment over and over, I learned about all kinds of interesting genetic stuff. I'm sure that's what it's for. I shouldn't be surprised that many people take what it says as gospel.
> I learned about all kinds of interesting genetic stuff
And there's much more to be found. The service of 23andme only records a limited set of SNPs. Further there is "multiomics" (see [1]), where not just the genome is sequenced but a complete biological fingerprint of metabolites is taken at different timepoints. This can e.g. give insight in onset of a disease even before any symptoms present themselves. I wonder when this will become available as a (mainstream) service, but I guess soon.
They're saying the testing medium itself made the test appear less scientific/accurate (to them) than it actually is. Perhaps if it had been a hair sample it would have appeared more scientific (again, to them).
Yah. I've got a 50% chance of having Huntington's. When my parent was first diagnosed with it, me + all siblings were immediately going to get screened. Half of us actually booked to get the test done. But we later cancelled our screenings, and we're all now rather we didn't know.
As I understand, genetic counselling in the case of HD is people telling you over and over again not to get tested. One of the constraints on fertility treatment if you're at risk is that you can't have any procedure that removes the potential baby's right to choose whether or not to be screened.
But in summary:
I've decided (having thought I definitely wanted to know) not to get tested. I'm glad there wasn't a button on 23andMe I could just click to find out. It's a complicated decision, should require some thought, and has life-changing consequences. While I'm strongly pro-choice, I also don't think 7-11 should be selling abortifacient drugs -- just because technology can make some decisions easy to execute on, doesn't mean they should be as easy as clicking a button.
I'd much rather that kind of thing be available as clicking a button personally. Getting information that could help you make big decisions is very useful.
What sort of big decisions does knowing you have Huntington's disease help you make? It's a debilitating disease with no treatment or any way to prevent it.
I plan my life expecting to live to an average age, as I assume most of us do. I save for retirement, I make investments that will pay off at times useful to me.
If I knew I had a serious condition that changes my quality of life and life expectancy, that means I need to change my life plans. Sure, it may not be 100%, but working off the most likely outcome seems sensible.
Not to mention, no treatments right now - if I know I've got something, I can follow developments and if treatment does become available, I can do something. Obviously, you could monitor this if you knew you were higher-risk anyway, without testing, but not everyone knows that.
Knowing about a chronic, untreatable, future illness can help you decide whether or not to have children, and if so, whether to have them earlier than you might otherwise have planned. Likewise it can influence you to accelerate the pace of other life plans (like traveling, or setting up a nonprofit in your neighborhood) and scrap other lower-priority plans.
That... seems pretty obvious to me, does it not to you? I don't know, I for one would knock back plans I might save for retirement to much earlier in my life.
Estate planning implications, savings implications, family goals...
Hopefully at the very least even without testing to go from 50% to sure knowledge, that 50% number is enough to get people to create wills/trusts. Save your survivors a lot of trouble with just a little up-front time and cost.
I completely understand you, because I'm in the same boat. It's hard to tell what is the right approach. I think that people should be tested. I'm still afraid to do that because I'm 31 years old and already started to experience some symptoms.
Yes, it's not easy decision but if you are not tested you can ruin life of your partner. It's better to prevent passing this terrible disease to your children.
Anyhow, 23andMe cannot tell you whether you have HD or not because they don't have sequences for that.
If anyone else is curious I found the following link that talks about why people wouldn't want to find out. After reading this I can understand why someone wouldn't want to.
Well, it's basically a death sentence for person having this condition. Event though there are some attempts by IONIS HTTRx to find a cure, currently, it's not curable. And it's hard to tell if this disease will ever be curable.
Life is a death sentence, unless someone has unlocked the key to immortality. I'm sure there are people who've lived less years than me who have still lived a fuller life than me. Randy Pausch, of Carnegie Mellon University, comes to mind:
Just because you're born knowing you're going to die doesn't mean we should all fret about it (unless you're a Nihlist of course, and then it doesn't matter as everything is futile). Knowing you're more likely to pass sooner would hopefully be a good thing in that you'd hopefully spend more time with your family creating memories than useless stuff like grinding at work and trying to climb corporate ladders only to become a senior middle manager in 20 years.
Personally, I would absolutely want to know to pivot my life towards reality. I'd much rather have an educated guess as to what my future might hold given the options vs sticking my head in the sand and "hopes and prayers" for the best. That being said, I can understand how it might simply be overwhelming for some people who wish to remain blissfully ignorant. Best of luck to them!
>One of the constraints on fertility treatment if you're at risk is that you can't have any procedure that removes the potential baby's right to choose whether or not to be screened.
Have you ever worked in tech support? Seemingly simple technical information can be very mystifying to people without good critical thinking abilities.
> I know a genetic counsellor who describes 23andMe's carrier screening tests as "the bane of their existence".
Do you really think a product can be built (for a reasonable price) which ensures that your genetic counselor does not get stupid questions from the consumers of the product?
That's like saying <My friend who works in tech support describes cheap computers as "bane of their existence">.
I'm not sure how I feel on this because I see both sides. If you're a doctor, you have to spend a lot of time addressing questions that are often based on other situations/conditions or aren't accurate because they were sourced on the web. At the same time, doctors were used to not getting questioned much and being able to do whatever they want for the most part. Last time I went in due to sickness they tried to do an x-ray which I declined. Many health care providers play the billing game and that's what they know. Now they have to listen to the patient and have more dialogue. Sometimes they are questioned. It's a shift. I think it's a good thing that people are asking more questions and doing research on their own. In real estate - automated valuations like Zillow provides are the "bane of their existence". Although many times it helps them because people want to seek an agent to sell because they looked up the Zestimate. If you're a professional - handling questions and concerns shouldn't be an issue.
Can we stop with the unsubstantiated heresay? What condition, what markers, what risk calculation is used?
I recently tried to research these companies to help a friend, and theres a huge amount of innuendo out there along with a lack of detailed and up to date information.
Even the companies seem to be in the dark. One example is I asked FTDNA to explain what the advantages might be to their autosomal only testing vs AncestryDNA's autosomal testing. A "senior" person there essentially said, we have no idea how they conduct autosomal tests so we can't help you.
Off the top of my head every company I can think of goes to great lengths to know the competition, in part to be able to explain their advantages to customers.
But not so for some of these DNA companies.
To be fair, AncestryDNA's web info was so marketing messaged I didn't even bother to ask them the question.
Have you got any opinion's on FTDNA's new myOrigins? I think it might make some things harder to interpret for people without very good genealogical records.
I have very weird metabolic problems... the US medical model --- if you can't diagnose it in two or three visits-- it doesn't exist.
I actually have the 23andme kit right here-- I plan to get the genome data to submit to some other services to see if there's ANYTHING I can learn about what's going on with my body.
Best of luck. If you really didn't have a diagnosis after 3 visits, you probably should see another doctor. I'm just curious, what you mean by metabolic problems?
I don't want to go into my medical history here... but I'm sensitive to several common proteins and compounds. Chronically low on B*, D and Calcium. Doctors think I'm nuts. It runs in the family-- my mother and grandmother have the same problem. B vitamins seem to modulate one of the problems and not another. :)
I'm surprised to see all the fear-mongering in this thread.
We leave genetic material behind everywhere we go. 23andme analyzes only a small subset of one's DNA.
The most important thing to realize about genetics is that very few health conditions (and even traits) are highly correlated with a specific genotype.
Some are, but the reason something like 23andme hasn't revolutionized health is because the correlations for most things are weak. 23andme does a good job of showing just how weak in the results. I'm 52% likely to have the eye color I have even though both parents have that color. I'm the tallest in my generation (in my family) yet my genes are mostly for below average height.
Over time, with a lot more data and a lot more correlation analysis with health and behavioral data, there will be more actionable information for the average customer.
As it stands, 23andme is useful for the following reasons:
- the data is entertaining. It's fun to find out how much neanderthal DNA one has, etc.
- the ancestry results are interesting.
- the health results make it clear just how little impact genetics has in most aspects of health. Yes there are some big exceptions, but those are a minuscule percentage.
By joining 23andme you get a chance to watch the studies unfold and plug in your own data. For a curious, patient person, this offers a great way to make an interesting area of science a bit more salient.
Your comment could also be taken as an argument for being a late-adopter of commercial genetic testing services:
1. The AUC (predictive power)for most traits is currently very weak
2. The genetic privacy protection landscape is currently quite volatile
Taken together this puts the consumer in the situation of having data that is of middling utility for them personally, but is of great potential utility for the testing company and insurers. A small increase over the average population susceptibility for trait X is often non-actionable for you personally, but over several traits might be sufficient to shift you into a different insurance risk class.
If you have privacy concerns and are interested in your risk profile for certain traits, look into whether a kit is available for those traits alone. You may wish to combine different kits from different providers to interrogate multiple regions (a more expensive strategy for the privacy-sensitive). There are a few companies that will put together a bespoke panel.
At present, it may be prudent to take a hacker approach to genetic testing.
https://isogg.org/wiki/List_of_DNA_testing_companies
These are good points. I'll respond with a few things that I think are relevant:
> an argument for being a late-adopter
Definitely. I was an early adopter of 23andme, and there is value to 23andme's research arm when a customer fills out the surveys, but the utility is low and comes predominantly in the form of entertainment. I'm the most neanderthal of everyone in my family who has signed up, which is a mark of pride.
> A small increase over the average population susceptibility for trait X is often non-actionable for you personally, but over several traits might be sufficient to shift you into a different insurance risk class.
While this is quite true, and would be very worrisome, I think the basic properties of heredity make it unlikely that the dystopian outcome you describe will occur. Here's what I think is the logical argument:
We are all very genetically similar. There are thousands of 5th, 6th, 7th, and more distant cousins of mine on 23andme. Chances are most of the population descended from Europeans are < 10th cousins away from each other, etc. The degree I state could be wrong but the general idea is true.
Broad, ethnicity-based risks are already known/used by insurers... things like sickle-cell risk, diseases more common among Ashkenazi jews, etc.
While there are many health conditions that correlate with genetics, their presence is dominated by chance. Thus we all have similar incentive for adverse selection of insurance, and hence insurance companies have little to gain by fragmenting their risk pool on the basis of tests with low predictive value.
Moreover, since so many people reproduce and thus take on financial responsibility for the genes of their children (which are subject to both hereditary risk and mutation risk) chance becomes an even more dominant factor in risk, and amplifies the incentive to create the largest risk pool possible because the risks cannot be predicted with high levels of accuracy. There have already been extensive, large data set statistical analysis of full genomes for predictive information about the top 5 most costly diseases. If there was going to be a large, statistically significant find, we'd have already heard about it.
The other side of this coin is that even people whose genetic scan shows reduced risk for all of the expensive diseases will still get those diseases with enough frequency that segmenting the risk pool will not make financial sense for insurers.
The situation we had a few years ago with respect to expensive pre-existing conditions was actually far worse. Type 1 diabetes is weakly hereditary and is dominated by chance. If you get type 1 diabetes you're looking at a few hundred dollars per month of cost for test strips, insulin, etc., to the point where for a middle class or lower middle class person, the disease can be financially crippling. Most people would prefer that the risk of randomly occurring, expensive diseases be spread among everyone, so that we'd all pay $1 more so that the person who gets unlucky and has type 1 diabetes gets the strips for free.
Yet in spite of this, even with acknowledgement of pre-existing conditions, the scenario remains. The insurance/healthcare industry has not managed to create the proper financial incentives that would insulate someone who drew the short straw and got type 1 diabetes from financial hardship (via pure insurance)... while it has failed to create any financial disincentive for adopting many behaviors that are nearly guaranteed to increase healthcare costs.
So I have hope that a better (broader, more public) understanding of genetic risk, random chance, and behavioral risk will help the insurance industry deliver products that allow all of us to save money based on things we can control, and not to be penalized for things we cannot control.
Neither of the extreme ideas (that there is strong genetic determinism for disease and healthcare cost or that there is zero behavioral/environmental impact) are true.
Also, fwiw, I don't think any of us would tolerate living in a society where people had to consider the genetic scan of a potential mate before deciding whether a relationship made sense financially. I realize this is the case today in some minority populations who have had (for historical reasons) lots of in-breeding) but over time the impact of that will be reduced.
Is there any way to just have your entire genome sequenced and get all the data in a software-friendly format? At that point there could/should be some open source software for analyzing it and finding common or well understood things like this. That way the software could be updated and people could re-run their analysis to look for newly discovered stuff.
I think this would be an awesome amount of fun. I for one would be interested in looking for certain gene variants that are not mentioned at all over at 23andMe.
Check out this series of articles from 2016 by Carl Zimmer [1]. He gets his genome sequenced by Illumina ($3100) and joins a medical study so that they'll give him the raw data. He gets the 70GB "BAM file" (Binary Alignment/Map) and passes it around to experts and they dig into it. Multiple weeks of computer time plus expert analysis---this is not a simple thing yet.
Have you already done a 23andMe analysis? If so, you can check out https://promethease.com/. It's exactly what you're looking for as they have constant updates that make it worth your while to rescan every year or so.
Promethease is awesome. I uploaded my 23andMe data to it and got back the kind of data I'd been hoping for in the first place.
Fair warning: the UI is very geeky. I think any HN reader should be able to find their way around without trouble, but I wouldn't recommend it to my non-technical friends or family.
23&Me will let you download a text file with the ACGT data, but only for the SNPs that it has. 23&Me does not sequence your full genome, so the SNPs available are a small subset of your DNA.
Prometheus is not open-source (I think), but all it does is read various files with DNA data (like the 23&me export), and match it up with the information in SNPedia (a Wikipedia-like open repository of what we know about certain SNPs), and then exports it to a pretty HTML/JS web report for you that you can download and save.
I did Illumina UYG. As part of that I got a 1TB hard drive with the nearly-raw files (BAM format with raw reads, VCF with variants).
Lots of people say " I for one would be interested in looking for certain gene variants that are not mentioned at all over at 23andMe." but they either never do anything with the data, or they look into it and realize that SNP analysis of gene variants is still a charltan's game.
For those interested in doing this, I will second parent. I have my full genome sequenced, and learned basically nothing that was all that interesting or actionable. It is very early days for DNA analysis.
I'm a bioinformatician, but haven't really pondered doing this on my own DNA too much. Wouldn't be terribly complicated to sequence and analyse your entire genome though.
Provided you could purify your DNA, sequencing wouldn't be an issue - just send it off to someone like BGI (Beijing Genomics Institute) and download the seq files when they're done. Purified DNA is stable and inert, so no special conditions required for posting it.
Sequence files are just text (if they're in FASTQ format), and all the common tools are open-source. No doubt someone somewhere has put together a Docker image with software for the entire workflow (FASTQ file processing --> read alignment --> variant calling), so processing isn't a big issue. As there's no de novo genome assembly or anything like that, the whole thing can be done on a run-of-the-mill PC, and would take a few days, depending on the depth of sequencing.
My guess is cost would be approaching US$1000 now.
Totally agree with everything you said, although I believe the price is closer to 500 than a 1000. I worked at a lab last year which did methylation analysis on rat genomes, and the price for sequencing was not nearly a 1000. Although the analysis was slightly different since they pulled out all the non methylated DNA, we still ended up with >50GB of 50 bp reads that had a decent coverage of the genome. I'm certain that whole genome sequencing would be easier than what I described.
I couldn't find any format that was neutral between vendors, so I wrote something (dna2json) that converts these vendor specific ones into a flat JSON file you can query easily.
If you are willing to let your DNA be publicly available online, check out George Church's Harvard-affiliated Personal Genome Project: http://www.personalgenomes.org/
The goal is to have a dataset of free and open genomic data so that scientists can analyze freely and avoid commercial silos of data.
They will sequence your entire genome for free, subject to a backlog caused by funding shortages.
I think you can pay $1,000 to jump to the head of the line. You may also be able to jump to head of the line if you meet certain "interesting" criteria, like willing to have multiple folks in your family get sequenced. Haven't looked into this in a while, so you'll need to check and verify this paragraph.
OpenSNP is for analysing your own SNP data, which you can download from services like 23andme: https://opensnp.org/
However, sequencing your entire genome is generally not available commercially. If you can find it, expect to pay at least a few thousand dollars for the raw data, and that's just sequencing reads that will need a lot of work to get to anything like a genome. Your best bet might be to try to join a genome sequencing research study and pre-agree to have access to your own data.
It's way less than that. They scan SNP's, of which there are about 10 million in total. So only 0.3% of the human genome varies between all of us. I think they only do the 602,000[1] most common SNPS, which is only 0.02% of the genome though they might do a few more.
A single error in the very large part of DNA that shouldn't vary per individual but "makes an ordinary human body with normal systems" means that you don't get an ordinary human body with normal systems.
Many such errors cause non-viable embryos, but if you have survived up to this point, then such a difference is still quite likely to have a meaningful impact to your health and is precisely the part that you'd want to have scanned and verified.
For adult DNA scanning we're not really interested in all the genes vary between all people and code for the color of your eyes, the melanine content of your skin, the shape of your nose or your height - but we are very much interested in, for example, scanning your genes that encode CFTR protein to check if you (or your kids!) will have issues with cystic fibrosis.
It's possible that you don't really have (or your kids are likely to not have) an "ordinary human body with normal systems" - that's what you'd need to find out.
>A single error in the very large part of DNA that shouldn't vary per individual
However true, that is irrelevant to genetic diagnostics as they exist today. We have no idea how a random error might impact health aside from very limited known mutations that are sufficiently frequent in the population to enable statistical correlation. We are probably decades away from being able to say, for a random mutation, 'this will lead to a deficiency in the synthesis of protein A which impact the development or working of organ B'. We can't even agree on the proportion of junk DNA.
This is helpful if you have rare symptoms with no currently available explanation - if you get a list of the "unusual" mutations that you have, and correlate it with the same data from the few people worldwide that have the same issue, you get a possibility to improve that condition.
I recall seeing cases of rare genetic disorders that have been diagnosed that way, by online communities sharing data.
http://matt.might.net/articles/my-sons-killer/ is one story that counters "this will lead to a deficiency in the synthesis of protein A which impact the development or working of organ B". For many parts of DNA we do know what protein it makes. For many proteins/enzymes/etc we have some idea about their function in the body - and if we have a test subject missing that protein, then the symptoms will be even more indicative about this, even if the population is tiny (1 in this example!) and doesn't allow for any statistical inference.
This means that if we really want to, we can try to find out the likely effect and possible workaround of a particular mutation, even if we currently don't have a ready-made answer for it.
That's right. I'm suggesting the average diagnostic test need only concern itself with those areas of the genome that are know to contain mutations that result in pathologies.
I think you said the same thing but in a clearer way.
I think the problem is that aside from a handful, they are not known. It's like saying you're only going to copy the parts of a program where bit errors are known to cause problems.
It's not that only 2% _can_ vary, it's that each person has about 2% different from the reference genome (and that 2% is different for every single person).
That's not at all true. For rare, undiagnosed disease we have to sequence the entire genome in order to look for the causative variants. For well understood (common) genetic disease we have small panels, but to say that only a small portion of the genome is informative is not correct. Additionally, there is no way to know a priori which loci will have the variation without sequencing the entire genome.
I think 23andme's genotyping is about 1% coverage compared to whole-exome sequencing, which itself sequences the ~1% of your DNA that codes for proteins.
One option is to take raw data from a service like 23andme and use imputation[1] to generate the missing data. This isn't as accurate properly sequencing everything, but it will get you more data to play with for free...
Are they still saying that by submitting a sample to them, that they then own your genome and can sell it to whoever they want? I'd love to get mine sequenced and check it out a bit, but not if they are going to sell it off to a million shady companies whenever they go bankrupt (maybe 50+ years, but still)
"We will not sell, lease, or rent your individual-level information (i.e., information about a single individual's genotypes, diseases or other traits/characteristics) to any third-party or to a third-party for research purposes without your explicit consent."
And...
"Unless you choose to store your sample with 23andMe (called consent to "bio-banking", which can be found here and changed in your settings), your saliva samples and DNA are destroyed after the laboratory completes its work, unless the laboratory's legal and regulatory requirements require it to maintain physical samples."
The "individual-level information" limitation is a huge weasel. 23andMe can and does share "anonymized" aggregations of its clients' genetic information [0].
Anonymization is not a property of a dataset though; it's a property of a dataset and the state of the world, and even if (and this is a big if) the dataset is truly anonymized right now, it won't always be.
Well said. Genetic data is by nature personally identifiable, and genomic disaggregation techniques can be expected to improve. Data troves like 23 and Me are an attractive target for DNA dragnets - at present, their SNP data is not CODIS-compatible (although it is theoretically possible that the SNAP data could be queried against a physical sample assayed for the same SNPs), but the physical samples are very valuable and customers should inspect their sample retention terms very closely.
Yeah, for now but in general, that's useless. They have the leverage to change the policy whenever they want as long as they notify the customers at the login screen and via email. And hey, they can change the policy to not even notify anyone. And of course, they can be bought out and the customer data is part of the company value so there's that.
Unless they provide an anonymous way of consuming their product I would never. ever. EVER. give a for-profit company my genetic data (and it's debatable who owns that data because last time I checked lawmakers don't really give a shit about information ownership unless it's about Hollywood) and have them tie it to my name. Fuck that!
Not only your genes worthless, since everyone has genes, but you leave them everywhere, like when you get a haircut.
Might be important if you were planning on a life of crime, or if you owe someone child support. But for the moment there's no good way to use them to make money off you.
There's a big difference between leaving your DNA on a cup and storing it in an easily-queried database. To collect your DNA from a cup , an interested party has to have an a priori interest in you specifically. To get it from a database (or databank, if 23 and Me is retaining physical samples, as their terms indicate they might), the interested party just has to have an a posteriori interest in "people's DNA", and hoover yours (and by probabilistic inference, your relatives') up along with everyone else's.
In the US, the protections against insurance companies using your genetic data against you are about as deeply entrenched as the protections against letting ISPs sell your internet history, and subject to much more intensive lobbying. Other countries have no protections at all - Canada's current bill is strongly opposed by the Trudeau government. Remember, even though most of these genetic risk scores are incredibly weak predictors, it is only necessary for insurers to believe they improve their actuarial models slightly to have a huge effect on differential insurance costs.
I mean, personally I think everyone should be prepared to start a life of crime. But hiding your genes is like trying to hide what you look like - basically impossible. Privacy is about not being able to associate people's actions with them, not hiding that people exist in the first place.
"unless the laboratory's legal and regulatory [...]"
That [...] could hide a lot of shady stuff being done via NSLs (etc.).
EDIT: There is a very interesting issue here, though, namely how the findings by 23andme are presented to their customers. There's good research that shows that presenting relative probabilities[2] (as opposed to just picking a sample size and doing everything in numbers relative to that) is very hard to understand for the general public (and even for statisticians unless they're paying close attention!). The Base Rate Fallacy is basically a consequence of presentation. Hopefully, 23andme are doing this responsibly, but I honestly don't know.
[2]: Example: "Eating X increases risk of cancer by 50%". Well, yeah, that might change my risk of cancer from 0.01% to 0.015%, but that that's not something I should worry about. Yet, we see these headlines because they grab people's attention.
After the Cloudera incident, I asked them to destroy my genetic sample and data. 23andMe's certification seemed clear that my data were no longer accessible by anyone.
I obviously don't understand the specifics, but if they are later owned by someone else, is that new someone considered a third party?
For instance, doesn't this mean that a hypothetical future 23andMe drowning in debit could be acquired by a company who could use the data for all sorts of terrible things without ever technically selling it to a third party?
This is what happened during the RadioShack bankruptcy iirc.
Instead of putting customer data up for sale they essentially just split off the portion of the company that held the data and put that up to be acquired.
I actually did some market research on creating a service to use 23andMe anonymously because of this worry (I'd call it 32andYou). Essentially the user could pay the service, and then the service would pay 23andMe. At higher paying plans you could pay for the swabs to be sent to a 32andYou shipping address so that 23andMe doesn't even have your mailing address.
Preventing 23andMe from directly linking a subject's genome to a name, cc, and mailing address would be nice, but what prevents them from comparing the test results to other subjects who have submitted samples? If my genetic relatives have also been tested by 23andMe then filling in the relationship graph doesn't seem too difficult, especially if given access to other social graphs. Does 23andMe offer certified isolated analysis?
good point, but on the short term at least, it would be pretty surprising if a sufficient amount of people took the test for that to be an actual preoccupation, lest you have reasons to think members in your family would specially likely to get the test (ie, history of genetic illnesses or a geeky uncle interested in biotech)
Ancestry.com currently has a big marketing spend on pushing their DNA service to determine a person's ancestral origins. The FAQ [0] implies that Ancestry operates their own lab, but who knows what happens behind the scenes or where that test is outsourced to (23andMe maybe?). Of course the more likely scenario is that the Ancestry test normalizes providing a sample in exchange for information that regular people would be amazed by. If the test from Company A could tell me specifically what my ancestral makeup is (which is something Americans in general are fascinated with), what can the test from Company B tell me about my health?
I mean sure, I could be way off, but I could also totally see any of my family members taking the test out of curiosity and I don't see any of them announcing it beforehand. I totally see the genealogy use case as a gateway drug to making this more popular.
A friend of mine did this when he used the service. Used the office of an acquaintance as his address, a fake name, and paid with a pre-paid Visa card that he bought in cash.
Yes, that's exactly what they are saying. That's how they make money. And if that concerns realize that your doctor sells your EMR data, your pharmacy sells your prescription data, the labs sell your blood work data too.
https://genos.co/ will do a 75x whole exome sequencing (very good quality even for a clinical test) for $500 with a good customer experience and they don't sell your data. You can then feed the data to https://www.promethease.com/ for interpretation.
> 75x whole exome sequencing (very good quality even for a clinical test)
You say that, but at the lab where I work, that level of quality would be a big fat fail - re-sequence the sample and get more data. They further describe their sequencing quality as "≥ 90% loci with 20x or more coverage AND ≥ 99% loci with 1x or more coverage". That's poor quality - very poor quality. We aim for 97% coverage at 20X and routinely get 98.5% They only get away with saying "Genos yields 50 times more data than comparable services" because they are comparing against 23andme, which uses a completely different test methodology.
Having a quick skim over that web page, yes it does look like they know what they are doing. However, they are still using SureSelect Whole Exome v4, when v6 has been available for quite some time now, and is so much better than v4. Their mean read depth is decent at 136X - that's about what we do. They quote a 31% pick up rate, where we have about 50%.
They talk about confirming variants using Sanger sequencing, but there is quite a bit of talk nowadays of stopping doing that, because NGS is becoming more reliable than Sanger. The problem with NGS is false positives, and the problem with Sanger is false negatives due to allelic dropout (the strand of DNA with the variant doesn't make it to the sequencer, so all you see is normal DNA). There is some concern that doing Sanger confirmation is rejecting more true positives than it is correcting false positives.
Our lab is both clinical and research. We don't do many research whole exomes any more - mostly doing whole genome instead.
You could mail me at nc74rmec@pliggle.homeip.net if you want. (Yes, that's a throwaway address.) Not sure I can advise you much though.
Is there a list of genetic services and what data they provide somewhere, maybe a comparison of sorts? My father recently passed away of arryhtmia and I'm looking for a way to determine if said condition is hereditary or not.
If you have concerns about a specific trait in your family history, I would suggest speaking to a genetic counselor. Many genetic conditions are influenced by a suite of relatively rare mutations not commonly included in commercial kits. A geneticist can tell you if this condition localizes to a specific chromosomal region or set of regions and sequence those target regions in depth for a better estimate of your risk profile. Perhaps more importantly, they can tell you if it is worthwhile to do so. Some conditions are too complex to reduce to effective testing, or result from poorly-characterized private mutations, but may have associated non-genetic biomarkers that your physician can monitor if you bring the problem to his attention. If your father's condition was well characterized and you have access to his history, you can do preliminary research on SNPedia (SNPedia lists whether a SNP of interest is included in the 23andMe kit), or do a PubMed search on "genetic risk factors" /"targeted next-generation sequencing" $condition to get a sense of the state of the art.
I ended up canceling my account because of this reason. That and the fact that a bunch of random people started trying to hit me up because apparently we were "linked".
I think people are forgetting to ask the key question - Cui bono? Who benefits?
23andme definitely benefits - all the data they have collected is very valuable, and they intend to sell it to pharmaceutical companies etc.
On the other hand, working in genomics, in my opinion the benefit to any one person having their genome tested in this manner is minimal. The simple reason is that most genetic alterations have low penetrance for phenotypes or involve complex interactions.
If you have already submitted a sample, you will get a report. Since 23andme maps your whole genome, they simply compare the existing data as new finding are approved. OR if you are like some and signed up early before the FDA crackdown, you already got all this information and now they are just reappearing little by little.
They don't go that far. A full genome sequencing costs around $2900 as of 2015. (Which is amazing, since the first one cost billions.) Maybe $1000 with the new Illumina HiSeq X Ten sequencing system. Data from a full genome sequencing is about 80GB. (Opportunity here for specialized compression - 98% of the genome for humans is the same.)
23andme is testing for about 100,000 known patterns using a much simpler approach for about a tenth of the price.
Lots of places. Genomics Personalized Health in Santa Monica offers the service to individuals for $2500.[1] Includes cloud storage for the data. They have a list of medical consultants who can help interpret the data; they just give you the bits.
23andMe uses genotyping. IANAMB, but I think that means they run a series of assays each of which "examines" a small PART of the genome to look for something very specific.
As part of their process, however, they could extract the DNA and keep a sample frozen for later assays or even full genome sequencing but I don't know if they do that.
I'm 99.9% sure that a new sample is not required. All of those risk factors can already be looked at with other tools which import raw data from your 23andme account.
Now they sell people only "ancestry" report for half the (now doubled) price. They probably don't get it, but I expect everyone on a "full" plan does. They already have the DNA info.
I got myself tested years ago with 23andMe and you do indeed get ancestry reports. I also get 'pings' every so often from likely distant relatives (3rd-5th cousins if anything).
One lady had been adopted as an infant and was desperately seeking any sort of relative who could tell her something about her origins. I told her what I knew about the families I am descended from but man did I feel bad for her. We were likely distantly related and I'm not sure my info helped, but that would be a pretty remarkable upside to genetic testing for people who want answers.
I was actually able to almost completely solve the mystery of where my great-grandmother came from (adopted as a baby in the South in the early 20th century) using genetic testing.
My opinion is that this test is useless at the least and dangerous at the most. It provides information that in almost the totality of the cases no one can correctly interpretate and transform in actionable health advice. Not scientists, not doctors, much less consumers.
But it is sold as a cutting edge scientific resource that will improve your life. It wont. Not even increasing the chance that you might avoid something somehow, that's the fallacy.
For our level of knowledge regarding causality in biology and genetics, I believe this test is as good as buying your astrological map.
> I believe this test is as good as buying your astrological map
Yeah, that's vastly overblown, sorry.
Let's say the average for the whole population of getting Disease X is 10% over a lifetime. You do the genetic test, and it turns out you carry an allele that's been shown with good confidence to raise that risk to 30%. What you get is not certainty, of course, but a place in a row of statistical buckets. There are studies providing solid evidence that Disease X can be typically delayed by years or decades if you do A, B, and C.
Is that information not valuable to you?
Note: I am in the general situation described above. Well, most people probably are, too, one way or another, they just don't know it.
EDIT: Perhaps you're confused because 23andme does not provide this kind of information now. But they did provide it in the past, before the FDA ban. Looks like the ban is now being gradually rescinded, one step at a time, which is good.
> There are studies providing solid evidence that Disease X can be typically delayed by years or decades if you do A, B, and C.
> Is that information not valuable to you?
It depends what A, B, or C are. If it's full mastectomy based on a misunderstanding of statistics then no, that information isn't useful and might be harmful.
Getting a double mastectomy is 90% effective in preventing breast cancer in high risk patients. Getting tested for cancer is 0% effective in preventing cancer. The best it can do is possibly increase your odds of survival.
Angelina Jolie wrote in an OP-ED about her choice to undergo a preventative double mastectomy.
Thanks to the 23andMe test I found out have I think 6 of 8 rare bad variants of various genes that give me what's currently estimated at around a cumulative 50% chance to develop a particular type of leukemia late in life. Of course, 23andMe doesn't provide this information - I came across it accidentally while studying my SNPs with other third party tools.
I don't really think about it that much - experimental treatments for it are already basically curing the disease and if I do get it it probably won't be for another 20 or 30 years. But now I can be the tiniest bit proactive - getting my CBC checked every few years, and watching out for unusual symptoms like fatigue.
The challenge is in communicating these things properly with fair analyses of the probability - we have X model that predicts Y risk, and we have Z error bounds on that. While it's unfortunate that most people lack the education to interpret statistical statements like that, I don't see why that should legally preclude me from getting information relevant to my health without a gatekeeper geneticist to hold my hand through "this variant has 1% prevalence, that means that 1 in a hundred people have it...".
This is the purpose of Genetic Counselling. A friend of mine does this and I can certainly see the value in having someone who understands the science walk you through the outcomes.
I see genetic counselors as gatekeepers to the information about our own bodies. Just give me my results and let me figure it out for myself. If some people want the service of a counselor let them get it but don't bar people from their own bodies.
We research other issues ourselves and the world hasn't ended. Imagine if you weren't allowed to read the Bible but had visit a "bible counselor" if you wanted to find out about things in the Bible. (I use that example because people make serious life decisions based on the contents of the Bible all the time. )
Not sure if you're trying to be ironic but that's exactly how it worked for many hundreds of years: remember that historically speaking, outside the Church most people couldn't read. One source estimates that in 1300 CE only 6% of England's population was literate! "Bible counselors", aka priests, were indeed the only way for most people to get information from the bible.
It didn't matter that they were literate, since printing a bible in english was still illegal. It was only in 1526 that
https://en.wikipedia.org/wiki/William_Tyndale
created the first bible in English, allowing the common folk to go around the 'Bible counselors'. As a result the church had him convicted of heresy and executed by strangulation, after which his body was burnt at the stake.
Do you believe that no genetic tests at all can be useful? Like, even for Huntingtons or Cystic Fibrosis? Or is it just these specific tests you don't trust?
soneca has a good point here (perhaps accidentally), which is that you'll notice that 23andme doesn't return Huntington's or CF results, and it sounds like the reason is because they would be so useful and predictive of disease.
Which does put 23andme's health results in this realm soneca described of "things that might be interesting, but can't be very actionable because they don't want to scare you by returning actually actionable information to you".
No. What's really happening is that they did provide a lot of probability estimates for some pretty serious stuff - back in the day before the FDA told them to stop doing it. I know because I carry a higher risk allele for a non-trivial disease (along with lower risk alleles for some other non-trivial diseases), and the test placed me in those corresponding statistical risk buckets which are different from the general population.
Then the FDA came down on them like a ton of bricks.
Now it sounds like they're reopening that door, slowly, step by step. I'm all for it.
>I carry a higher risk allele for a non-trivial disease (along with lower risk alleles for some other non-trivial diseases), and the test placed me in those corresponding statistical risk buckets which are different from the general population.
>23andMe said my most elevated risks — about double the average for women of European ethnicity — were for psoriasis and rheumatoid arthritis, with my lifetime odds of getting the diseases at 20.2 percent and 8.2 percent. But according to Genetic Testing Laboratories, my lowest risks were for — you guessed it — psoriasis (2 percent) and rheumatoid arthritis (2.6 percent).
>In the case of Type 2 diabetes, inconsistencies on a semantic level masked similarities in the numbers. G.T.L. said my risk was “medium” at 10.3 percent, but 23andMe said my risk was “decreased” at 15.7 percent. In fact, both companies had calculated my odds to be roughly three-quarters of the average, but they used slightly different averages — and very different words — to interpret the numbers. In isolation, the first would have left me worried; the second, relieved.
I agree with your assessment of the situation, but I'd still be very surprised if e.g. a Huntington's test shows up in 23andme, and I think that's because the FDA doesn't trust consumers to react appropriately to receiving serious and actionable information from 23andme.
> the FDA doesn't trust consumers to react appropriately to receiving serious and actionable information from 23andme
So, that is an interesting and valid point. I've thought about it myself. Seems like these tests are something new, and it may take a while before the new thing is absorbed into the culture and it's treated the way it should. Yes, there is still the risk of misunderstanding the information you're getting.
There are also a few simple solutions - e.g. any doctor should be able to help you correctly integrate this information.
23andme actually does return Cystic Fibrosis results. They just don't in the US due to FDA regulations.
I'm Canadian and have access to the full list of 23andme's health results. I actually found out that I have a recessive CF trait. Not 100% sure that its correct, but definitely something that I'm going to check out before having kids.
I'd much rather have known about that now, than after having a kid with CF.
I am a total layman in biology, genetics, and health, so I have no broader or deeper opinion at all on the subject. I specifically don't believe that this 23andme (or similar) test is any good for your health or useful at all. And selling it as such is dangerous.
On articles that I read on the subject (the subject of 23andme tests, not genetics in general) and my own capacity for acquiring information and transforming them into learnings and opinions that I form to better live my life.
This test was extremely useful to me, as I found out I was a carrier for a previously unknown genetic disease.
It was because I used 23andMe that I now know I am a carrier and can potentially prevent having a child who would suffer from this disease. I'd say that was worth 200 bucks.
23andme can only detect common variants. In general, common variants do not cause non-mild diseases - certainly nothing worth avoiding a child being born. You should certainly not be making decisions like that based on a report from 23andme.
It can detect whatever variants they put on the SNP chip, be they common or rare. The only caveat is we have to know what variants to put on the chip in the first place. That's the hard part, linking rare variants to disease. After that link is made, the rest is easy.
Is it a sure fire shot to detecting all rare genetic disease? Of course not.
Is it a good way to become aware that I am a carrier for a rare mendelian genetic disease? Yes. Very much yes.
They still have to have good clustering of samples for each variant they are testing. That is, there needs to be a sufficient number of samples in each of the three states (homozygous normal, heterozygous, and homozygous variant) for the software to look at the analogue signals and draw a box around each of the three clusters. This generally prevents the analysis of rare variants using chip technology.
I would be very curious if you could look up the variant that 23andme have reported you have on http://exac.broadinstitute.org/ and let us know the "Allele Frequency" from there.
The thing is, most people are carriers of several rare mendelian diseases. When we do whole exome sequencing, we get on average a couple of hundred rare potentially pathogenic variants in each patient, of which possibly 20 or 30 are actual causes of rare mendelian disease. However, the patients are only carriers of these disease, and are completely irrelevant to their health. The likelihood of them having children with someone who is a carrier for the same condition is very slim (but something we investigate every day).
For the particular SNP I am heterozygous for in this particular gene, the population level allele frequency is 0.00001649. Missense mutation. Another variant in this gene, a stop loss, is at 0.0017
Yes, of course the likelihood of it being a problem is slim, but definitely not zero. High enough that it is worth knowing.
This is the state of just about every trendy consumer health product. My watch tells me my heartbeat? Great. What the hell am I supposed to do with that information?
I agree with this to a point. Obviously, genetic information can be quite informative for non-complex traits or diseases caused by variants in only 1 or a few genes.
The reality is the genome isn't the complete instruction set for what makes you you. The interaction with the environment dataset is missing, along with any heritable epigenetic information. Add to that, our understanding of function is still extremely limited. We still don't really understand how one gene generates different proteins (via alternative splicing) at different rates. Or how gene expression is so finely regulated at a cell-specific and sub-tissue-specific level. The list goes on. Rules that seem to apply to one gene or gene family don't apply to others.
One day, we'll likely get there, but that day is still some way off. For that reason, I see no great reason to have my genome sequenced at the moment, though it'd be reasonably trivial to do so.
> Obviously, genetic information can be quite informative for non-complex traits or diseases caused by variants in only 1 or a few genes.
And (unfortunately) those are the exact variants that services like 23andme do not detect.
23andme uses an array chip. These only detect common variants, in locations that have been pre-planned while designing the chip. A batch of patient samples are all tested together, and the probe for each variant produces a signal. Software then tries to cluster samples into three groups, which are homozygous normal, heterozygous, and homozygous abnormal. If the variant isn't common, then there would not be a decent number of samples in each group, and the clustering would fail. These tests are literally incapable of detecting any variant that is rare.
To detect rare variants, you need to do proper sequencing, for example with Sanger (single gene), or high throughput sequencing (AKA NGS, Next Generation Sequencing). This can be targeted panels of selected genes, whole exome sequencing, or whole genome sequencing.
A disease caused by a variant in a single gene (a monogenic disease) is usually caused by a rare variant. The more severe the disease, the more rare the variant is. A gene may have loads of common variants that do not cause disease. A gene may have a really rare variant that does not cause disease. Or it may have a rare variant that does cause disease - but this needs to be determined by someone with training and experience in the field.
As a lab, we regularly get inquiries by people saying "I have a variant detected by 23andme in <known disease gene> - could this be causing my <rare genetic condition>?" The answer is "No - this test is incapable of detecting disease-causing variants - it only detects the benign ones."
My entire family dies of strokes, and 23&M identified me as having a blood clotting disorder. This is extremely valuable to know in terms of basic lifestyle modification (e.g. being even more sensitive to deep vein thrombosis on long flights), and in being able to discuss prior to things like surgery.
Can't wait till the require these for health insurance... Seriously, is there regulation protecting people from "pre-existing conditions" discovered by their genetic analysis?
Of course, this article is about New Zealand, but I will not be surprised to see similar things in the States. Thankfully ACA provides protection for health insurance, but we're already seeing things like https://www.congress.gov/bill/115th-congress/house-bill/1313.
No, the FDA thinks it can decide whether someone can sell a product claiming to diagnose disease. Because, fairly explicitly in the Food, Drug, and Cosmetics Act, it can, and, in fact, is obligated to.
23 and Me gives you the raw genetic report. If you're sophisticated enough to not panic and jump out a window because you have some terrible disease, the assumption is you can also find open source data and/or software that will give you this same information.
The problem with what 23andme was doing is going direct-to-consumer with tests that were potentially sketchy. If you're willing to risk sketchy information you can find all kinds of bleeding edge research on your particular genetic makeup and choose how to handle it.
Adults can't handle misleading and inaccurate health information, and are known to spend large amounts of money to e.g. literal snake oil peddlers back when peddling snake oil as a cure-all wasn't prohibited.
Yes, we are regulating who's allowed to tell people that a relative is going to die, and we're asking people who do so to show evidence that they know what they are talking about. If someone would go around selling a service "is your relative going to die" by guessing or simply telling what they want to hear, then that should be regulated and prohibited.
As another poster said, "One problem is that they warn that your offspring are at high risk for some condition, when really "high risk" means 0.5% higher risk than the general population. The other is that they may say you are not a carrier for a certain condition, when they only test for one variant of it, where proper tests will test for multiple variants."
If you tell people "we ran a test for X and it was positive/negative" then you'd better be able to show that whatever rituals you performed actually lead to reasonable information about X. Simply having a test that has some information related to X (e.g. if it would be used together with other factors to diagnose X or not X) doesn't mean that you can honestly describe it as "test indicating a high risk of X" - it may be that this particular test is indicating that, and it may be that it (alone) is misleading, and we need someone (e.g. FDA) to draw a line.
I found some useful information in my 23andme report regarding poor or undesirable responses to quite a few pharmaceuticals, my phase 1 metabolism is... novel...
There are already companies out there using DNA sequencing for some absolutely bullshit products...Vinome comes to mind, they suggest wine you might like based on your genome.
Personally, I'm all for it though. It's a way to have fun with science. As a scientist, it's nice to have stupid "horoscopes" to keep life interesting.
I guess these are different reports, but I know a genetic counsellor who describes 23andMe's carrier screening tests as "the bane of their existence". Those reports seem not-so-easy to understand based on the patients she sees.
One problem is that they warn that your offspring are at high risk for some condition, when really "high risk" means 0.5% higher risk than the general population. The other is that they may say you are not a carrier for a certain condition, when they only test for one variant of it, where proper tests will test for multiple variants. They can both scare and soothe irresponsibly.