The Promethease option

Ever since 23andMe stopped providing health information to new customers as the result of a disagreement with the federal Food and Drug Administration,¹ readers have been scrambling for options to obtain basic information about how their genetic makeup may be affecting their health risks.

By this time, here as we close in on the fall of 2015, most readers seem to have an understanding that they have options, but still have questions about the option most commonly used by genealogists — Promethease.

The Legal Genealogist wrote about Promethease last year² but it’s clear that folks are still confused. For example, reader Gwen Digby wrotethat she was “interested in family ancestry and medical information. Is Family Tree DNA the best source for this, then transferring the info to Promethease for medical info?” while a reader using the moniker “Just Curious” was also interested in testing “for family tree and medical reasons” and asked, “As I understand it, 23andme is best test for this and then import the raw data into Promethease (please confirm).”

Let’s start with some basics.

Promethease is “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.

So… which of the big three genetic genealogy companies is the best to test with if what you want is medical information? For genealogy, of course, I’ve already given my recommendations (start by testing at AncestryDNA, transfer your raw data into Family Tree DNA, then test with 23andMe to be sure you’re fishing in all the ponds).⁷

If what you want is medical information, then here’s what I know about the differences among the companies.

This morning, I ran my own results from 23andMe, AncestryDNA and Family Tree DNA through Promethease. And the differences are very apparent when you do that.

First, in terms of how long the reports took, there was a difference, and it isn’t at all clear why the difference was so stark:

Family Tree DNA
Waited 11 seconds
Runtime 5 minutes 25 seconds

23andMe
Waited 45 seconds
Runtime 9 minutes 25 seconds

AncestryDNA
First run
Waited 3 seconds
Runtime 40 minutes 2 seconds, then failed
Second run
Waited 40 minutes 5 seconds
Runtime 7 minutes 29 seconds

So be prepared to wait, depending on what company you’ve tested with, and perhaps depending on time of day, server load and the like.

Second, and more significantly in terms of choosing a testing company if what you want is health information, there really is a difference in how much data you can get. This is because 23andMe in particular is skewed towards testing for medical information, while Family Tree DNA deliberately excludes known medical markers — making it much the best choice for those who only want genealogically-relevant information and don’t want to risk disclosure of health data. The key difference is in the number of genotypes annotated, meaning the analysis available of the two alleles inherited for a particular gene⁸:

Family Tree DNA
11487 genotypes annotated

AncestryDNA
13007 genotypes annotated

23andMe
23284 genotypes annotated

Breaking this down by the numbers of alleles reported as good results, bad results and not set (a category meaning that scientists don’t know or aren’t sure if the alleles have any health implications), here are the numbers:

Family Tree DNA
Good 1,261
Bad 166
Not set 10,070

AncestryDNA
Good 1,538
Bad 255
Not set 11,225

23andMe
Good 5,281
Bad 413
Not set 17,613

In short, you’re going to get a lot more information using your 23andMe raw data than if you use the raw data from either of the other two companies, and more if you use your AncestryDNA raw data than if you use the raw data from Family Tree DNA. Comparing AncestryDNA’s bigger lists of negative results rather than Family Tree DNA’s results, I see that AncestryDNA’s data will show me that I have an elevated risk of type 2 diabetes and of atrial fibrillation and cardioembolic stroke. And using 23andMe’s results rather than AncestryDNA’s, I find out that I have an increased risk of endometriosis and am a carrier of hemochromatosis.

Oh joy.

Now seriously remember that interpreting any of these results is far more difficult than getting them. I have a whole slew of results no matter what report I look at, 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. So… What to make of all this?

There’s help available in understanding your results once you get them. First and foremost, read the Promethease help page, starting with the section “How to read a Promethease Report.” You can also read up on Promethease, including:

• “You Can Transform Your Genetic Ancestry Data Into Health Info, But Your Results May Vary,” by Dr. Barry Starr of Stanford University at KQED Science.⁹

• “Promethease – Genetic Health Information Alternative,” by Roberta Estes of DNAeXplained.¹⁰

• “My 23andMe Results: Getting a (Free) Second Opinion,” by cdwScience of the My Biomedical Informatics Blog.¹¹

• “How a Wiki Is Keeping Direct-to-Consumer Genetics Alive,” Antonio Regalado of MIT Technology Review.¹²

And you might want to join the Promethease Users Group on Facebook.

Now… remember… each of these three reports costs $5.00. You can buy one, you can buy them all. And And understand that before you do anything else at Promethease, you’re going to have to sign off on a set of disclaimers:

Before you may use Promethease to retrieve information about the human genome, you must read and agree to the following statements. Please read each statement and check the box next to each one and then click ‘I Agree’.

• I understand that the information provided in my Promethease report is based on SNPedia.com and that my report is for educational and research purposes only.

• I realize that most published reports about DNA variations explain only a small part of the heritability of a trait, and they also don’t take into account how different variants might interact. In addition, published reports typically ignore environmental, dietary, microbial, medical history and lifestyle factors, any or all of which may well affect my true risk for any trait or disease.

• I am aware that I am strongly encouraged to discuss my Promethease report with a doctor, genetic counselor or other health-care provider prior to making any medical or reproductive decisions. I also acknowledge that I am advised to confirm any significant finding discovered in part through the use of Promethease by an independent, clinically validated test for use in connection with the medical trait in question.

• I have read and understand the Privacy Policy and the Legal Terms and Conditions of this website. I agree to these conditions.¹³

Promethease. A healthy choice for those of us who still want health information. But one that takes some work to understand.

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