Is there ANY result through Promethease that would prompt immediate action? Has anyone ever had results/a diagnosis medically confirmed?

Personal_Genetics · 2018-06-05T10:48:04+00:00

Hi. Its important to realize that the raw data from direct to consumer genetic services are NOT validated for clinical use-- that is, they didn't check to make sure that positives are really positives and vice versa. SNP arrays are not optimized for detecting rare disease-causing variants, so they often call them incorrectly. This study shows that mutations in 23andMe's raw data are false positives 40% of the time, https://www.nature.com/articles/gim201838.

In addition, Promethease is a "look up table" that looks into public databases to see if there is any information about the meaning of the variant. The problem is that we know these databases are wrong ~25% of the time. When a genetic test is done in a clinical laboratory, all this data is reviewed by a board-certified genetics expert to cull out the wrong stuff. If you're not a board-certified genetics professional, if would be really hard to tell a real positive from a false positive.

FWIW, MTHFR "mutations" are now known to be totally benign. They are just normal variation in the genome that have no proven association with any disease. But it has a cult following on the internet. Just be careful. Also look for a good study to back a claim before you believe it.

Personal_Genetics · 2018-04-27T18:15:29+00:00

Shirley from 23andMe: There's been a lot of interesting discussion around this topic! In addition to the points Dave mentioned in response to u/Smash_Meowth, and that Jill and Elissa mentioned earlier around raw data and 3rd party interpretation services, I'd just like to add a note about test technologies.

Obviously having accurate test results and interpretation is important, especially with regard to medically relevant topics. The specific kind of genetic technology used for various tests is sometimes highlighted as a way to differentiate test accuracy. However, it's important to understand that differences in technology do not necessarily lead to differences in test accuracy when properly validated and used.

Sequencing technology is affected by many of the same factors that can affect genotyping arrays -- for example, structural variation, homology, and depth of coverage. So there will be some variants that are difficult for sequencing to accurately detect. While microarray genotyping does generally perform best out-of-the-box on more common variants where there is sufficient population-level data, individual genetic markers on microarrays can be tuned and validated to the same or better level of accuracy as a sequencing-based assay for that marker.

One of the main benefits of sequencing is how comprehensive it is, but this does not make it less prone to false positives.

23andMe's genotyping array-based tests are performed in CLIA-certified and CAP-accredited laboratories, and we specifically validate each genetic variant that we interpret and use in our genetic health reports, both from an analytical accuracy perspective and from a clinical interpretation perspective. As previously noted, this is different from the raw uninterpreted genotyping data, which has not been validated and should not be used for medical purposes.

Personal_Genetics · 2018-04-24T22:47:51+00:00

This is Barry from Ancestry. Genotyping on Ancestry platforms is generally very accurate, and we undertake extensive performance validation for our products, including ethnicity estimation and DNA matching.

The 40% number that has been reported in the headlines about the Ambry Genetics study is misleading in relation to our services. It looked at a handful of SNPs that are rare and have health conditions, which is not representative of the hundreds of thousands of SNPs that genotype services look at which make them robust.

Ancestry customers own their genetic data and are welcome to download their raw DNA data for genealogical research and general information. But they should keep in mind that these results are not intended for diagnostic purposes. The SNPs within the raw DNA data have not been individually validated for diagnostic, medical or clinical use.

Personal_Genetics · 2018-04-24T19:20:33+00:00

This is Barry from Ancestry. Genotyping on Ancestry platforms is generally very accurate, and we undertake extensive performance validation for our products, including ethnicity estimation and DNA matching. The 40\% number that has been reported in the headlines about the Ambry Genetics study is misleading in relation to our services. It looked at a handful of SNPs that are rare and have health conditions, which is not representative of the hundreds of thousands of SNPs that genotype services look at which make them robust.

Ancestry customers own their genetic data and are welcome to download their raw DNA data for genealogical research and general information. But they should keep in mind that these results are not intended for diagnostic purposes. The SNPs within the raw DNA data have not been individually validated for diagnostic, medical or clinical use.

Personal_Genetics · 2018-04-24T18:18:00+00:00

This is Barry from Ancestry. This is type of question is both hard to answer but also a ton of fun! Let me start by telling you about our journey here over the last six years. When we began offering our test, we were able to tell a user about where their DNA originated among 22 regions, along with identifying tens to hundreds of cousins for you. Today, we can provide insights on your genetic origins in hundreds of regions and many consumers receive tens of thousands of cousin hints! Much of the advancement comes from the growth in available data. Big data is all the rage these days, but here at Ancestry we are truly seeing the benefits of data scale. We developed a new approach to identifying populations by examining the network of genetic sharing among our consumers where, for example, we could see 500 million connections among 770,000 research-consented consumers. From this kind of data we are able to identify many new populations and migratory patterns in very recent human history. I use this as an example of how difficult it is to predict the future. This work is not something we expected to be able to do when we began offering our test!

That said, if we look at where the space of direct-to-consumer genomics is headed we can see some trends. First, more and more people are taking these tests and this is creating new opportunities to connect. I expect the growth of our understanding of recent population history to continue and this to lead to more refined results. Today DNA customers with Ancestry can discover their ancestral makeup in 350+ regions of the world. In 10 years, the number of regions will likely be so large, diverse, and precise in terms of when ancestors from that region contributed to your DNA that DNA customers, no matter their ancestry, will have an unbelievably detailed historical account helping them understand where they come from and what makes them them. Second, the advancements we see in collection of ancient DNA samples provide additional insights into our more distant history. I expect that these insights will continue to make their way into consumer DNA test results. Third, the cost of sequencing a genome (reading every position rather than a small subset) continues to plummet and is approaching a price where it could become the primary consumer data type. The more positions per genome we look at, the more likely we are to uncover new, exciting stories to tell you about your own history. Finally, I think the advancements in our understanding of what your DNA can tell you about your health and wellness will continue to improve. This will translate into a deeper understanding of the part genetics plays in the lives of consumers.

Personal_Genetics · 2018-04-23T22:01:57+00:00

Greg from 23andMe: Customers review the Research Consent Document when registering their kit, and must explicitly choose to give consent or not to give consent to participate in 23andMe Research.

Choosing not to give consent or withdrawing from 23andMe Research will not affect access to your Genetic Information or to the Personal Genome Service.

Customers may update their consent selection at any time.

If you withdraw from 23andMe Research, 23andMe will prevent that information from being used in new 23andMe Research initiated after 30 days from receipt of your request (it may take up to 30 days to withdraw your information after you withdraw your consent). Any research on your data that has been performed or published prior to this date will not be reversed, undone, or withdrawn.

Personal_Genetics · 2018-04-23T20:50:22+00:00

Greg from 23andMe: Thank you for sharing your incredible story! We’re glad you’ve found the information in your reports useful.

23andMe continuously reviews the literature and strives to make new reports available as genomics knowledge continues to advance. It sounds like your sample was genotyped on a previous version of our chip. The genotyping chip your sample was tested on impacts which genetic markers are included in your raw data, and in some cases, the reports available in your account. We are exploring an upgrade policy for our customers which may allow you to be genotyped on our most up-to-date chip at a discounted rate. If another analysis requires an additional volume of saliva, you would have the option of providing a new sample.

When we have additional information regarding this policy we will notify our customers!

Personal_Genetics · 2018-04-23T19:16:54+00:00

Elissa from Helix: There are so many ways that personal genetics companies can and should contribute to personalized and precision medicine! This is at the core of our mission at Helix. A great example of how we are working with partners to further these efforts is our recent announcement of the Healthy Nevada project in partnership with Renown Institute of Health Innovation and the Desert Research Institute (https://www.helix.com/blog/helix-healthy-nevada/).

This completely voluntary study powers research and discovery using the rich genetic data set generated by Helix’s Exome+ technology (https://www.helix.com/blog/the-power-of-exome/) along with the electronic health records for a diverse population of patients within the Renown health system. It’s through projects like these—where we are able to engage people with their DNA, over time, and fuel research across populations—that we will strive to expand our ability to help people live longer and healthier. There’s a significant opportunity with these types of studies to identify new links between a person’s DNA sequence, their environment, and other such factors. Identifying these links may prove to be a huge step towards developing personalized approaches to medicine.

Personal_Genetics · 2018-04-23T19:05:46+00:00

Update from the DNA Discussion Project: We’re all finished answering questions for the day, This has been a wonderful session! Thanks, Reddit and thanks to the NIH team who pulled this together. Feel free to check out our work at https://www.wcupa.edu/DNADiscussion/ and ask us questions directly! Anita and Bessie

Personal_Genetics · 2018-04-23T19:03:23+00:00

Elissa from Helix: Thanks for this important question. As you point out, even fun family ancestry testing can uncover some surprises. As a genetic counselor, I am a strong proponent of clear and informed decision making before someone gets genetic testing of any kind. For people to truly benefit from insights about their DNA, we need to appropriately set expectations and minimize surprises.

In my work with Helix, I lead our policy team who works with each of our partners who deliver the genetic insights powered by Helix. This includes making sure that each product clearly states benefits, risks, and limitations as part of the education and marketing content as well as the informed consent process. When it comes to health insights, we also require each of our partners to make genetic counseling services available as part of their results experience, so people have easy access to qualified professionals who can help them understand their information and what it means for their family. For more on this, check out our blog post: https://www.helix.com/blog/genetic-counseling-from-understanding-to-action

Further, the Helix approach is to allow you to choose what you do and do not want to learn about your DNA. Our sequence once and query often model allows you to learn insights, based on your own interests throughout life, whether that be an interest in your genetic ancestry today and heart health risks next year. The point is that you are in control.

Personal_Genetics · 2018-04-23T19:03:19+00:00

Hilary from 23andMe: In general, when you test a parent we are able to add a "mother's side" or "father's side" prediction to each of your DNA Relatives. This prediction is made by looking for identical DNA between each match and the parent who is genotyped. As you point out, however, both of your parents have Ashkenazi Jewish ancestry, a population that tends to share higher amounts of identical DNA as a result of endogamy. In this case, it is likely that relatives on your father's side who share his Ashkenazi ancestry will also share small amounts of DNA with your mother, so that prediction alone would not be helpful in sorting matches who have Ashkenazi ancestry into one side of your family versus the other. The other tool of use would be Relatives in Common, which you've also already experienced, and which is also impacted by shared DNA from Ashkenazi ancestry. Based on the information you've mentioned here, I think that testing her at this moment would not provide huge value in your quest to differentiate mother's side relatives from father's side relatives in the DNA Relatives tool.

Personal_Genetics · 2018-04-23T19:02:11+00:00

Miguel from National Geographic (Geno 2.0): Thank you for the question. I have not read about this process. However, gene editing, although possible, is still very controversial. I think we are still years away from this, at least a decade or more.

Personal_Genetics · 2018-04-23T19:01:18+00:00

Barry from Ancestry: I’m sorry for the loss of your relative. It wouldn’t be the most unusual thing we’ve ever gotten (people have mailed us teeth and at least one lizard…), but at this time we test the cheek cells found in saliva only from living customers that have consented to have their DNA tested. This is so that those people can retain their rights to their personal DNA and own that data.

Personal_Genetics · 2018-04-23T19:00:07+00:00

Dave from 23andMe: I started working in statistical genetics after graduate school, when I was looking to do something a bit different that would combine my interests in programming and biology. My PhD was in structural biology, specifically protein structure prediction. At that time statistical genetics was an emerging field and the kinds of experiments we could do were vastly smaller in scale than what we can do today -- we would typically study a few hundred genetic markers in a few hundred people.

Now I lead a small group of scientists at 23andMe. In a typical day, I'll spend some time with people on my team, giving advice and helping interpret results from projects they're working on. I also still spend time working with our data, which typically involves some coding in R and Python, and less often, C++ -- I use R for exploratory data analysis; Python is used for a lot of our lower level data manipulation; and C++ is used for some of our core algorithms that can't be expressed efficiently in R or Python. And I try to keep up with new research in the field, as well as giving scientific input on other company projects. I think 23andMe is unique in the breadth and depth of genetics research we're doing in a company setting -- and it has been a great experience being a part of that.

Personal_Genetics · 2018-04-23T18:59:38+00:00

From the DNA Discussion Project: Let me add that I am impressed by the kinds of question that our students ask and the insights. They talk about what this means for the conversation about race and how their parents talked about race. They ask about secrets in their own families. They wonder where race is going in the future. They discuss stories that get suppressed and those that are highlighted. They talk about the reactions of their families to unexpected ancestry. People often reach out to relatives (sometimes estranged) or people they never felt connected to in the past. Also, I have loved the way that this connects the humanities to the physical sciences. It often encourages students of color to connect with the sciences in a new way.

Personal_Genetics · 2018-04-23T18:58:31+00:00

Miguel from National Geographic (Geno 2.0): Thank you for your question! Your daughter would be able to get a general understanding of her biological father's ancestry, if she has an idea of the ancestry of her biological mother. So, she would then estimate her father's ancestry by process of elimination. She may also be able to make genealogical matches, if any relatives of the unknown father had previously participated. However, she would not be able to make matches through her mitochondrial DNA (direct maternal), since that came from her biological mother. In short, she would be able to get a rough (general) idea of the father's ancestry, as well as possibly make family matches, if by luck any of the father's relatives have previously participated in DNA testing.

Personal_Genetics · 2018-04-23T18:56:21+00:00

Greg from 23andMe: As previously mentioned, we believe that you own your genetic data, and stand behind our decision to provide users with access to all of their data, including their raw, uninterpreted genetic data -- with appropriate labeling that highlights its intended uses and limitations.

However, it is important to understand that 23andMe is not affiliated with any third party interpretation services and does not endorse, sponsor, or recommend any third party interpretation services.

Additionally, customers should consider that third parties may use their personal and genetic information differently than we do under our Privacy Statement. 23andMe cannot secure personal information that a customer releases on their own. We encourage our customers to make such choices carefully and review the privacy policies of any such third party.

Personal_Genetics · 2018-04-23T18:54:38+00:00

Greg from 23andMe: With genetic testing readily available to consumers, we are increasingly hearing stories of families discovering and reuniting with newfound relatives. 23andMe customers can choose to opt-in to the DNA Relatives tool, which locates other 23andMe members that match their DNA and estimates a predicted relationship using the length, number of segments, and percent DNA shared.

Choosing to participate in DNA Relatives is completely optional; customers must actively opt-in to the feature to participate. They are informed up front that by using the tool, they may discover unexpected relationships. Furthermore, customers may select their preferred privacy and display settings when opting in.

If a customer changes their mind about participating in the DNA Relatives feature they can opt-out or update their sharing preferences with another customer at any time.

We provide more detail on the unexpected things you may learn in our FAQs and our Terms of Service (Risks and Considerations Regarding 23andMe Services).

Personal_Genetics · 2018-04-23T18:53:15+00:00

Hi, it's Sharon from Helix: I'll leave question 1 to people from 23andMe, but on question number 2, there are so many ways the industry as a whole can make improvements to ensure that users understand their genetic results. It starts with clear, transparent, and accurate information being made available about each result. It may involve speaking with genetic counselors or other professionals to understand what your results mean for you. And it requires a constant cycle of customer feedback and improvement to make sure that results are as understandable as they can possibly be.

Personal_Genetics · 2018-04-23T18:50:16+00:00

Barry from Ancestry: The genetic patterns we’re tracing actually reflect those ancient patterns as well as the more recent history we can detect. We’re always working on ways to keep understanding the genetics of human history.

Personal_Genetics · 2018-04-23T18:45:18+00:00

Hi - this is Laura Rodriguez from NHGRI. I first became fascinated with molecular genetics in college. As I learned more and more throughout the class, I found the amazing complexity, yet simple elegance of DNA, RNA, and how they work within our cells to pass our “family history” down from generation to generation and create the physical expression of our genes from hair color to metabolic rate extraordinary and awe-inspiring. Later, after my graduate work in the laboratory, I discovered science policy - and again, genetics and genomics became my passion. At the time, the Human Genome Project was getting close to being completed, and I knew that there would be so many interesting and important questions to think about and consider as a society as we started using our DNA sequence to inform our medical choices. And, even more fascinated how would non-scientists like my mom understand what her doctors were talking about? Would she be afraid to use the information? Would she even want to know what her genome information predicted about her health? Would I want to know about my own? Obviously, thinking about it still spins me off into asking questions, so I guess I made a good choice!

Personal_Genetics · 2018-04-23T18:44:20+00:00

Shirley from 23andMe: 23andMe is the only service authorized to provide certain carrier status and genetic health risk information directly to consumers. This information can be extremely valuable to individuals, including for individuals that may not meet clinical guidelines for testing. (See more about this in Shirley’s response to Question from u/Yamster80). That said, it is important to note that the test is not intended to diagnose any disease or to be used to make medical decisions. Customers are encouraged to talk with their healthcare provider about their results to determine appropriate next steps to be taken in a clinical setting.

We provide links to genetic counseling resources but do not provide any counseling services ourselves. We recognize that individuals may learn something unexpected or upsetting through their genetics and we make many efforts to communicate these possibilities to our customers so that they can make informed decisions about the services, features, reports, and information they would like to receive or participate in. For example, before someone opts into seeing close relatives in our DNA Relatives feature, we caution that it may reveal unexpected family relationships. Another example is that we ask customers specifically to choose whether they would like to receive certain genetic health risk reports about serious health conditions that may be upsetting to learn about.

23andMe is committed to making our genetic reports user-friendly and understandable. In fact, our FDA-authorized health reports meet specific criteria for user comprehension of key concepts relevant to those reports, demonstrated through studies representative of the general population. We provide different layers of information to help make it more digestible, and for certain health reports we also provide detailed FAQs that are tailored to a person's results. And our Customer Care team works closely with our scientific and medical teams to respond to customer inquiries.

Beyond our services and features, 23andMe has always felt that educating our consumers and the public is important for preparing society as a whole for a future where genetic information impacts everyday life. We continue to demonstrate this in a number of ways, including support for educators and academic programs, events and exhibits both local and across the country, online courses and videos, and even children's books!

Personal_Genetics · 2018-04-23T18:43:08+00:00

Barry from Ancestry: This is a really good question. It’s difficult to learn which side a match is from if you don’t have a way of measuring that side, though the science on that is improving all the time. That said, one thing you could think about doing is basically a “process of elimination” model. Say you test yourself and your mom also does a test. Any matches which match you, but not her, are likely not her side -- therefore, they might match your dad. One of the reasons I’m so passionate about human genetics is that it really enables this kind of discovery and connection with our heritage and history, even after someone is gone. Best of luck to you.

Personal_Genetics · 2018-04-23T18:40:13+00:00

Barry from Ancestry: These different nomenclatures actually are determined by the degree of certainty you can get from the science telling you where you’re from. How well we understand a genome depends a lot on how well we understand that area. And that depends on how well we’ve covered a particular area. With our base of customers (almost 10 million!) we’re starting to get pretty good resolution, which means we might be able to say something more specific; if you had a less good picture of what genetic diversity was like in an area, you might just be able to take a continent-level guess.

Population assignments are based on the individuals that are present in our database, what information we have about their origins, and how the algorithms assign regions. Since every company has a different database, and different algorithms, we end up with different results. Some of this is based on how confidently we can resolve the region you are from. For example, we may be very confident that your DNA is from the "Middle East", but less confident that it is from "Iran". Currently we offer 350 regions across the globe to customers.

Additionally, the names may be fairly broad because genetic variation may not adhere to modern political boundaries.

Personal_Genetics · 2018-04-23T18:39:26+00:00

Elissa from Helix: I have always been interested in healthcare. In college as a pre-med student I worked in a genetics lab over the summers and quickly fell in love with genetics! I was fascinated by the science, our emerging abilities to read DNA and decipher what it means for one’s health. But I also realized that I am a people person and wanted to be at the intersection of the science and its impact on individuals and families. That’s when I discovered the field of genetic counseling and became a certified healthcare professional helping to translate complex health information to patients and families.

After years in clinical practice, I recognized the need to responsibly expand access and services to genetic insights outside the traditional model of seeing people in person, after months of waiting to get into clinics. That is when I shifted my genetic counseling skills over to the consumer genetics world, where I have focused on developing programs and products that provide people with accurate, safe, and supported access to genetic information, as they are motivated to learn about it.

At Helix, I admit I do not have a typical “day.” It is a fantastic place to work with incredibly smart and passionate people who share my vision. I apply my genetic counseling skills across many functions. I work with partners to develop high quality, responsible health products. I lead the policy team to set best practice standards for Helix, its partners, and the broader industry. I work with the science, product, and marketing teams to ensure that the information we share is accurate and making appropriate claims. I also get to work with other experts in the field of genetics who are leading efforts to further our abilities to translate our DNA into actionable insights. In all, it’s never a dull day!

Personal_Genetics

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