Using Promethease
There isn’t a week that goes by that The Legal Genealogist doesn’t get the question from a reader somewhere.
It’s usually someone dealing with an unknown parentage situation, but not always.
And the question is very simple: “how do I get information about my health history using DNA testing?”
That’s an easy question.
It hasn’t got an easy answer.
Oh, you can go to your doctor, discuss doing genetic testing, and pay the associated lab and doctor fees for whatever testing you can convince the doctor to order and get the information that the doctor or a genetic counselor is willing to explain to you.
That’s probably the easiest way to do it, and certainly the recommended way for anyone who has a specific identifiable health concern that needs to be addressed.
But for those of us who are just curious… who just want to see what information may be lurking in our genes without any particular need for an answer right now… DNA testing does offer some options.
One choice is to test with the genetic testing company 23andMe. Its $199 Health + Ancestry Service option provides some health reports that let you get information (at the moment) about some 41 carrier status variants, 22 trait variants and seven wellness variants that the company reports on. The carrier status variants include things like cystic fibrosis; the trait variants things like sensitivity to bitter tastes; and the wellness variants things like lactose intolerance.
But there’s another, much less expensive option, and it’s open to anyone who’s tested with any of the genetic genealogy companies.
It’s called Promethease: “a literature retrieval system that builds a personal DNA report based on connecting a file of DNA genotypes to the scientific findings cited in SNPedia.”1
I’ve written about this option before,2 but it seems a good time to revisit the issue now that 23andMe is offering an Ancestry-only version of its test.
So… what is Promethease? It’s “a computer program developed by the SNPedia team which allows users to compare personal genomics results against the SNPedia database, generating a report with information about a person’s attributes, such as propensity to diseases, based on the presence of specific single-nucleotide polymorphisms (SNPs) within their genome.”3
It “builds a personal DNA report based on the scientific literature cited in SNPedia and a file of genotype (DNA) data. Customers of DNA testing services (23andMe, FamilyTreeDNA, Ancestry.com, Complete Genomics, …) can use it to retrieve published data about their DNA completely independent of whichever company produced the data.”4
SNPedia, in turn, is a wiki devoted to the medical consequences of DNA variations, including software to analyze personal genomes. It describes itself this way:
SNPedia has been launched to help realize the potential of the Human Genome Project to connect to our daily lives and well-being.
Our genes are important, and the variations in them help define our uniqueness. Yet at the same time they help forge links between us, as many of us carrying certain variations find ourselves facing similar medical issues. SNPs are those variations. SNP stands for Single Nucleotide Polymorphism and means variation in the same place (polymorphism) within the DNA sequence.
SNPedia is based on a wiki model, in order to foster communication about genetic variation and to allow interested community members to help it evolve to become ever more relevant. We anticipate that as the cost of genotyping (and especially of fully determining your own genomic sequence) continues to drop, we’ll all want to know more – a lot more – about the meaning of these DNA variations. And SNPedia will be here to help.5
What Promethease does is compare your raw autosomal DNA test data — and you can use your raw data from any of the three major test companies (Family Tree DNA, 23andMe and AncestryDNA) — to information collected from peer-reviewed scientific journals at SNPedia to “create a personal report linking your DNA variations to the information published about them.” It’ll cost you a whopping $5.00 to get each report.
Among the specific DNA markers (called SNPs, or single nucleotide polymorphisms6) it looks at are ones now believed to raise the risk of Alzheimer’s disease, influence baldness, determine sensitivity to anesthetics, trigger obesity and type-2 diabetes, impact the risk of coronary heart disease, or result in lactose intolerance.
There are currently 87,905 SNPs in the SNPedia database and — depending on which genetic genealogy testing company you tested with — a Promethease report will give you links to any scientific studies on markers in your DNA. According to SNPedia:
• Ancestry.com uses Illumina OmniExpress Plus, reporting all SNP’s on that chip for $99. Current users will receive data for about ~47,000 of the SNPs in SNPedia. ~25,000 of these are in ClinVar. Prior to May 2016, Ancestry customers received data for around 13,000 of the SNPs in SNPedia with only a few hundred from ClinVar. This test is currently available in the USA, Canada, Australia, and the UK.
• 23andMe $99 “ancestry only” product, which does allow downloading of full results, e.g. to Promethease to get a report, or, $199 “ancestry + health” product, which includes carrier status reports (and also full data download). One time payment, lifetime membership. Both products uses the (same) customized Illumina chip which covers 25695 of the 87905 SNPs in SNPedia. Less than 2,000 of these are known to be in ClinVar; presumably some of the proprietarily named “i-SNPs” correspond to ClinVar/SNPedia entries as well but 23andMe does not reveal which publicly or to its non-corporate users.
• FamilyTreeDNA Family Finder uses an Illumina OmniExpress for autosomal ancestry testing for $99, including partial raw data download. It covers 13,193 of the SNPs in SNPedia, with ~2,000 of those being known to ClinVar.7
So in terms of coverage, it’s current AncestryDNA, then 23andMe, then older AncestryDNA, then Family Tree DNA.
To begin in any case, you need to download your raw data:
Steps to download AncestryDNA raw data:
1. Log in to Ancestry and go to your AncestryDNA Home Page (DNA -> Your DNA Results Summary).
2. Click on the Settings link on the right hand side.
3. Choose Download Raw DNA Data from the Actions menu on the right hand side.
4. Enter your Ancestry password and click on the box saying you understand the downloaded copy is yours at your risk. Then click on Confirm.
5. Go to your email account. You’ll get an email with the subject Your request to download AncestryDNA raw data. In the email is a link, Confirm Data Download. Click on that link. It’ll take you back to Ancestry.
6. On the Ancestry page that loads is a link: Download DNA Raw Data. Click on that. Then choose the location on your hard drive to save the zip file that results.
Steps to download 23andMe raw data:
1. Log in to 23andMe and drop down the Tools menu. Choose Browse Raw Data. If you haven’t done so before, choose the Raw Data Opt-In by clicking the I understand link.
2. At the top of the page, find the download link either in the tab at the top or in the sentence “You can view or download your data at anytime…” Click on the download link.
3. At the bottom of the Download Raw Data page, choose what DNA data you want. (For Promethease, you want All DNA) and then re-enter your 23andMe password. Then clock on the Download Raw Data link box. Then choose the location on your hard drive to save the zip file that results.
Steps to download Family Tree DNA raw data:
1. Log in to Family Tree DNA. Drop down the myFTDNA menu in the top.
2. Choose Family Finder and open that menu, then choose Download Raw Data.
3. From the bottom menu, choose the type of DNA raw data file you want to download. For Promethease, the recommendation is the Build 37 Raw Data Concatenated file. Then choose the location on your hard drive to save the file that results.
Once you have your raw data file, head over to Promethease and carefully read the agreement. Read the privacy policy and the terms and conditions before just clicking the check boxes.
If you agree, then check the check boxes, click on I agree, upload your raw data file and pay the $5 fee for the report. You’ll get a notice within about 10 minutes that the report is finished.
Now… this isn’t easy. Interpreting any of these results is far more difficult than getting them. There is a video that will help you understand how to use Promethease and Reddit discussion groups for questions about Promethease in particular and about SNPedia in general.
And it isn’t medical diagnosis — it simply isn’t the same thing as being told you have a disease or condition. I have a whole slew of results, starting with a SNP that provides “an apparent resistance to several diseases such as invasive pneumococcal disease, bacteremia, malaria, and tuberculosis” on the good side, followed by one that poses “an increased breast cancer, type-2 diabetes, and aggressive prostate cancer risk” on the bad side. But these are risks, not diagnoses.
But for anyone who’s just curious about what medical information might be lurking in your genes, it’s a fast and inexpensive option.
SOURCES
- “Promethease,” Promethease.com (https://www.promethease.com/ : accessed 19 Nov 2016). ↩
- See Judy G. Russell, “A health data option,” The Legal Genealogist, posted 13 July 2014 (https://www.legalgenealogist.com/blog : accessed 19 Nov 2016). Also, ibid., “A healthy choice,” posted 13 Sep 2015. ↩
- ISOGG Wiki (http://www.isogg.org/wiki), “Promethease,” rev. 8 Aug 2016. ↩
- “Promethease,” SNPedia (http://www.snpedia.com/ : accessed 19 Nov 2016). ↩
- “SNPedia:About,” SNPedia (http://www.snpedia.com/ : accessed 19 Nov 2016). ↩
- ISOGG Wiki (http://www.isogg.org/wiki), “Single-nucleotide polymorphism,” rev. 4 Oct 2016. ↩
- “Testing,” SNPedia (http://www.snpedia.com/ : accessed 19 Nov 2016). ↩
Judy, thank you! I was trying to decide what to do today. This will be it!
It’ll keep you busy and out of trouble! 🙂
Busy – yes. Out of trouble – never. 🙂
🙂
I did this for both my dad and me. The results were fascinating. For example I responded really well to one medication and it’s because I have a somewhat rare variant of a certain SNP. I also have a SNP variant which implies an incredible sensitivity to another med. I’ve never taken it but my mother has and she had a lot of problems with it. My dad did not have that SNP. Either a mutation or I got it from my mom. When I get my mom’s DNA results, I will most certainly be doing the Promethease thing with them.
I compared my results to my dad’s using Excel and now I am pretty certain which parent to blame for which of my health issues 🙂 Thanks for the migraines, Mom!
Done just now. Already finding this information fascinating! Thank you again!
I am not really impressed with Promethease. It tests CYP (cytochrome P)2C19 for drug metabolism; however, what about the other cytochromes that affect drug metabolism? I recommend reading “Tolerating Uncertainty – The Next Medical Revolution?” N Engl J Med 375;18, 3 November 2016, pp 1713-15. The article concludes with a quote from Sir William Osler “medicine is a science of uncertainty and an art of probability”. I would not bet the farm on my results in Promethease because they just point to uncertainty. Promethease can do what they do because they are not under the auspices of the US Food and Drug Administration.
> however, what about the other cytochromes that affect drug metabolism
Can you suggest any drug metabolism genes Promethease does not report information on?
The ones available can be found at http://mayoresearch.mayo.edu/center-for-individualized-medicine/drug-gene-testing.asp
There are many more Cytochrome not yet available. Cost is a factor for Promethease as for any lab.
In SNPedia, the easiest way to search for a gene is to type it into the search window. In Promethease, there’s a search window as well as a scrollable ‘pull-down’ listing all gene names.
The majority of the 60+ CYP genes, i.e. all those that we know to be associated with (credible) pharmacogenomic literature, are represented, and the compilation is updated regularly based on both literature review and community suggestions and edits.
Thank you, Judy, for your informative blog. I have learned so much
from following it. I appreciate that you welcome comments and
engagement from readers and hope you and your readers will be open to
hearing what I have to say about Promethease. I have stayed mostly
silent on this topic, at least publicly, to this point.
If you were used to paying $500 for your car insurance each year, and someone said, “Well here! I can give you car insurance for only $5!” you would think to yourself there must be a catch, right?
The same is true with Promethease. There is a catch.
Before I go further I will state unequivocally I SUPPORT PEOPLE HAVING ACCESS TO THEIR RAW DATA. I am a member of the genetic genealogy community and have seen first-hand the value of third-party tools and raw data files. I am also a genetic counselor and I provide counseling on genetic health results professionally. I am not anti-raw-data-access. I am pro-reliable-genetic-health-information which is not, in my opinion and experience, available using raw data files at this time. This includes Promethease, which by the way states in its user agreement the information is for “educational and research purposes only” (i.e. not to be used for medical purposes).
As a GC who has worked one-on-one with many clients using raw data for purposes such as Promethease I have developed experience, taken note of issues with the raw data and genetic reports, and have significant concerns. At this point I do not recommend clients pursue the health tools on raw data, however I will provide consultation to someone who has already done it and is coming to me for support/interpretation.
1. Genetic testing for health purposes typically is repeated by the clinical testing lab after a positive finding. This repeat testing is to confirm positive findings, which sometimes are no longer present when re-tested. Sometimes the same technology is used and sometimes a different DNA technology is used. The reason for this is that the process of going from biological sample to computerized data is a complicated process and not always smooth or error-free. This is one of the reasons why both 23andMe and Promethease state that the information they provide is for “educational and research use only.”
2. The labels used by Promethease — “Good repute”, “Bad repute”, and “Not set” — can be and are being interpreted incorrectly, at no fault of the user/customer. I raised my concerns to Promethease staff earlier this year. I maintain a list of SNPs which I feel are “misclassified”. Someone who has the common version of a SNP for early-onset Alzheimer’s disease instead of a rare protective version should not see “bad repute” on their report for that SNP. This causes unnecessary alarm about an increased risk for early-onset Alzheimer’s disease which is not even present.
3. SNP technology leads to no-calls and flawed readings. Even in the clinic/hospital setting there are errors with SNP testing. I had a client report she was a carrier of Smith-Lemli-Opitz syndrome based on her Promethease report (this is a rare but severe syndrome in childhood) and when I researched her SNP at the primary source used by Promethease (the SNPEdia database) it was reported that these reports of SLO carriers were miscalls if discovered using 23andMe raw data. This has happened with other conditions and genes (TP53 and BRCA1/2, for example).
4. The Promethease tool treats each SNP as an individual. In reality, genes, variants, proteins do not act as “islands” so to speak — they are interacting at every level possible (within a cell, within a tissue, within a body system, between body systems) in a complex manner that we do not understand at this point in time. Looking at one SNP in isolation and attempting to make conclusions is not feasible. Even a high-risk BRCA variant identified in the clinical setting only leads to breast cancer in 87% of cases. Why? There is much more to health and disease than one single variant in the DNA.
5. Clinical pharmacogenomics testing often takes into account more than one SNP/variant at a time. When pharmacogenomics labs such as Kailos Genetics looks at results to predict how a person might react to a statin drug, for example, they consider the findings of at least three genes. The combination of variants in those three genes is then used to make an assessment of how the individual may respond to a statin. Promethease reports (and most clinical testing labs, for that matter) do not take into account the complex interaction of multiple SNPs or variants. This is only one example of how a Promethease report may lead you to believe you understand how your genetic profile affects how you process certain medications when it may not in fact be true.
I can support my assertions with cases and have other genetic counselors reporting these issues to me as well. This is not new information to those who work in the genetic health sphere, but because third party tools exist outside of regulation, nothing is being done about it. I feel in a quandary as you can imagine.
I will repeat I am not opposed to people having access to raw data files or genetic information in general. As I stated recently in a radio interview, I have faith in people being able to understand once given the chance to learn how to read a complex genetics report and being guided in how to research more deeply. I am strongly opposed to the guise of reliability being perpetuated about Promethease reports as “medical” information.
To not speak up at this point feels like a betrayal of my personal ethics and morals. I respect the time and hard work of Mike and Greg at Promethease, and I am not attempting to undermine their efforts to help people access genetic information. There is inherent weakness in using raw data for genetic health information if that raw data has not undergone any type of confirmatory analysis. I am not okay with the false reassurance and unreliable genetic risk assessments being provided to customers at this time who are using raw data to attempt to glean health information.
A good next-step would be to request that companies and projects providing customers with access to raw data take responsibility to provide information about what use of raw data is responsible (and what is not) when they provide customers with access to the file. If you would like to join me in these efforts, please reach out through my website or email me.
Thank you for reading through to the end.
All very good points, and why I keep stressing that “this isn’t easy…. And it isn’t medical diagnosis.”
I have a rare mutation (1 in a million) carried on the y chromosome that can cause blindness in a male child if two people with the same mutation get together. Would Promethease detect this. I am interested to know if this can help me confirm more distant ancestors on the paternal line.
You’d have to review the literature to see if this particular gene is reported. Start here: https://www.snpedia.com/index.php/Promethease
Brianne- Thank you for that excellent detailed explanation. Your information on the raw DNA for medical understanding really helped me to understand the process and all its flaws. I have chosen not to go beyond the fun of knowing my ancestry. Thanks again.
Having had breast cancer (with no familial history [2 years cancer free]), I would very much like to have this sort of analysis done … if it were actually what it purports to do. I also have a PhD in Botany, so I get the genetics. I appreciate what you have said, and I think I’ll wait a while on that health assessment.
I do molecular phylogenetics, and some of the genes we worked with were thousands of bp long. 1 or 2 loci out of thousands isn’t exactly a representative sample!
We constantly advise people that DNA is not destiny, and direct-to-consumer tests are not clinically validated tests. We’ve also responded in the past to Ms. Kirkpatrick; it’s certainly possible to cherry-pick cases supporting any position, but the larger issue is whether we should have easy, online access to the scientific literature about the DNA variants we carry. We believe we should, and so SNPedia is freely available 24/7, and like Wikipedia, there is a dedicated community of researchers (and counselors) helping to keep it as up to date and accurate as possible.
We are also pleased that we can now refer Promethease users for consultation with certified genetic counselors should they wish it, and we value and incorporate the advice we receive from these counselors since it helps to improve both SNPedia and Promethease.
I must say I love reading all of the comments here about raw DNA and all the ins and outs to it. This is good for anyone who has undergone this way of knowing or is thinking about it. Love the input as well from the genetic counselor who does this for a living. It is appreciated and important. I wanted to Thank all of you for your important input in this area. I look at it as it is still very much in its infancy form and with all of your input it will help it to grow into something so much more and let us hope positive for all who take part in it. I myself wanted to tell you how important this information is for me and my family. My mother was adopted. Most people can grow up and know what makes them well them. What they might have to look out for in their daily health lives. We did not have that luxury. So even though I realize the results of my promethease report may never become fruitful it is nice to know what to keep an eye on. It is also important for me to be able to look at my children and be able to tell them what possibly they might inherit. In fact shortly after I got my results from my ancestry I ran into promethease and decided to upload my raw dna for their data on me, my mother two wks later suffered a Pulmonary embolism. The drs. and hospital ran tons of tests and determined it to be hereditary due to a blood clotting issue. I went back to my promethease report and sure enough there was the sneaky lil gene in red that I over looked thinking it was the least of my concerns. Plus as I know not all mutations will actually turn into the disease. With the climate of our nations health insurance issues and the fact that it is becoming all to clear many of us have no choice but to take our health care into our own hands. That also means finding the least expensive way of ensuring our health is taken care of. My reports to me are just a roadmap to follow if I find I have issues. Thank you all and keep up the good work. Never under estimate how important everything you do is!
Glad you got useful information from this.
Thank you for the very helpful summary of how many SNPs are covered in SNPedia and ClinVar for each company!
I’m sure the question has been asked and answered a million times since Relative Finder was started: Does FTDNA redact health-related SNPs from the data they allow you to download? Is that part of the reason FTDNA has so few hits in SNPedia?
No, they don’t redact anything from what you’re allowed to download; it’s more a feature of the SNPs that are chosen for sampling. FTDNA focuses on SNPS that are genealogically relevant and works to exclude those that are medically relevant. That’s why it’s really the best choice for families that want to focus on genealogy and have family members who are worried about what testing might disclose.
Do you know anything about the raw data received from the free Genes for Good research project? I have heard that they use the same lab as 23 and Me but I’m not sure whether it’s the same test. I ran my unphased file through Promethease for fun and found it super interesting (it was interesting but not surprising to find that I’m homozygous for one of the Celiac-related genes; of course my dad will deny he could possibly have contributed and blame it all on my mom). Is it worth paying for another service to get more data or am I pretty much set with what I’ve got?
I recognize none of this is diagnostic. I just think it’s fun and interesting. “Entertainment Purposes Only.”
I don’t, I’m afraid. I’ve read through the info on their website briefly but don’t find an easy answer for you.
So does this mean for health research AncestryDNA is better than 23andme’s ancestry and health service?
I mainly want to figure out which supplements to take to help prevent whatever diseases and conditions I’m predisposed to.
NONE of these tests are designed for the purpose you’re trying to use them for. If you want genetic testing for health supplement guidance, you’re better off consulting with a doctor or genetic counsellor.
I ordered the AncestryDNA Test on sale for $59. Apparently the raw data can be fed to different sites to get that info
I too am a genetic counselor and understand the points made by both Brianne and Judy. I, however, feel it is beneficial to have a site like Promethease available to consumers. True, many do not clearly understand what they are getting in their report, but they often seek more information from others–health professionals as well as other consumers. They become better educated about their own health and are requiring health professionals to learn more about genetics and health in order to answer their questions. I think everyone benefits in the long run.
I have no problem with the site being available. My only issue is in ensuring that people know what they’re doing before they do it.
I do love the wealth of information provided in my Promethease report (I used 23andme raw data). While it is lengthy and complicated to interpret, I was pleasantly surprised by the detail and sheer enormity of the document. Wish I did more research to avoid paying the full price for health AND ancestry knowing now that I can get that analysis elsewhere for much cheaper. I also did Xcode’s (www.xcode.in) nutrition analysis for an easier to interpret report. It gives food suggestions for vitamins and minerals I tend to be deficient in and a lot of easy to understand explanations throughout this thorough report. Great service for the price for those looking for something easier to look at. Richards – U.S.
I’m sorry I chose to use Ancestry.com as I later found that many websites will only interpret 23andme data. I know promethease will do it but it’s kind of difficult to find really useful health info there, IMO