<img decoding="async" class="alignright size-medium wp-image-5403" src="https://blog-api.23andme.com/wp-content/uploads/2009/11/Picture-209-300x225.png" alt="" height="125" srcset="https://blogcms.23andme.com/wp-content/uploads/2009/11/Picture-209-300x225.png 300w, https://blogcms.23andme.com/wp-content/uploads/2009/11/Picture-209.png 408w" sizes="(max-width: 300px) 100vw, 300px" /> 
<img decoding="async" class="alignright size-medium wp-image-1059" title="dnacode" src="https://blog-api.23andme.com/wp-content/uploads/2008/08/dnacode-300x224.jpg" alt="" height="125" />
by David Hinds
A small study conducted by researchers at the Cleveland Clinic and reported at last week&#8217;s American Society of Human Genetics annual meeting found that family health history (FH) often gave different assessments of cancer risk than SNP-based personal genomic (PG) risk assessments obtained from <a href="http://www.navigenics.com/" target="_blank" rel="noopener noreferrer">Navigenics</a>. The results have been characterized in the popular press as demonstrating that FH is superior to PG in predicting who is at increased risk of disease. We believe that research in this area is important, but felt that the conclusions of the study were not necessarily supported by the study&#8217;s design. 
What is family history risk assessment?
An identifying feature of many genetic diseases is that they tend to &#8220;run in families&#8221;.  Families also tend to share similar environmental risk factors. Collecting health information about family members can thus provide important clues about an individual&#8217;s risk of disease. Family history risk assessment is typically performed by genetic counselors using structured methods so that the results can be easily compared with guidelines for relating history to disease risk. There are also <a href="http://www.hhs.gov/familyhistory/portrait/index.html" target="_blank" rel="noopener noreferrer">online tools</a> for recording family histories, and <a href="https://familyhealthlink.osumc.edu/Notice.aspx" target="_blank" rel="noopener noreferrer">some disease risk calculators</a> can take advantage of this information.
Family history is known to be especially helpful for identifying individuals at substantially elevated risk of disease because their families carry rare, high-risk variants (such as mutations in BRCA1 and BRCA2, for breast and ovarian cancer).
<h6>What is SNP-based risk assessment?</h6>
SNP-based personal genomic risk assessment is currently based on results of studies demonstrating that specific common genetic variants are correlated with disease risk. These common variants generally have small effects, but in aggregate, may contribute to more cases of disease in the population than rare variants like BRCA1/2.  Navigenics and 23andMe use similar methods for combining information from multiple markers to arrive at an estimate of an individual&#8217;s risk.  As with family history, SNP-based tests only account for a subset of risk factors, and are most informative for the subset of individuals whose estimated risk is substantially different from the population average.
Some personal genomics services, such as 23andMe, include variants other than common SNPs in their risk assessments. In the future, personal genomic risk assessments may routinely apply technologies beyond SNP-based genotyping to form a more comprehensive picture of an individual&#8217;s genetic landscape.
<h5>What did the study show?</h5>
The researchers identified 22 patients in a genomic medicine clinic who either had cancer themselves or a family history of cancer, and their spouses. All 44 received FH assessments, as well as the Navigenics SNP-based PG risk assessment. There was generally poor agreement between the FH results and PG results. In addition, five of the 22 patients were later found to carry high risk mutations for an inherited form of colon cancer, but were not identified as high risk by the PG test.
<h6>What does this really mean?</h6>
The inconsistency between FH and PG observed in this study is largely due to a fundamental difference between the two types of tests. Family history is most effective at identifying individuals with familial cancer syndromes related to rare mutations with large effects, while SNP-based tests use common variations with smaller effects. The two types of tests are thus measuring very different things.
The two methods also may not be assessing the same underlying conditions. There is no doubt that individuals with <a href="https://en.wikipedia.org/wiki/Hereditary_nonpolyposis_colorectal_cancer" target="_blank" rel="noopener noreferrer">hereditary nonpolyposis colorectal cancer</a> or <a href="https://en.wikipedia.org/wiki/Familial_adenomatous_polyposis" target="_blank" rel="noopener noreferrer">familial adenomatous polyposis</a> have a different spectrum of disease than typical colon cancer patients. Familial syndromes also represent only a small proportion of all cancers (5% of all colon cancers).
Furthermore, the Cleveland Clinic study started from the presumption that FH was the &#8220;gold standard&#8221;, so any deviations in the PG results were considered errors. In our opinion, this is not an appropriate starting point for performing a head-to-head assessment of test performance. Such an assessment would, ideally, evaluate the accuracy of the two tests in a set of individuals not previously screened for a positive family history, as some of the participants in this study were.
Perhaps the most troubling suggestion from the study was that individuals at high risk based on family history might choose a PG  test, and be misled by a result indicating they were at low risk. 23andMe disease risk reports all discuss the limitations of the tests and the importance of family history as well as other environmental and undiscovered genetic risk factors.  The suggestion also neglects any benefits of PG testing for the large majority of individuals who do not have a positive family history of disease.
<h6>Where do we go from here?</h6>
At 23andMe, we are committed to increasing scientific knowledge of the genetic basis of human diseases and traits, and we are conducting research to evaluate and improve the predictive accuracy of our genetic risk models. As we learn more about the genetic factors underlying disease, genetic information should become increasingly valuable in developing risk assessments, and will be complementary to methods such as family history. Ultimately, we believe that the path forward will involve integrated, individualized risk assessment based on family history, personal genetics, and environmental risk factors.

23andMe Blog

23andMe Blog Team

Family History and Personal Genetic Risk Assessments: A Perspective on the Cleveland Clinic Study

<div>
<img loading="lazy" decoding="async" class="alignright size-full wp-image-7758" src="https://blog-api.23andme.com/wp-content/uploads/2010/11/ashg601.jpg" alt="" width="300" height="155">
By Kim Barnholt and Amy Kiefer
It’s an exciting week for 23andMe! A number of our research scientists have headed to Washington, D.C. to showcase some of our research discoveries at the annual meeting of the <a title="ASHG" href="http://www.ashg.org/" target="_blank" rel="noopener noreferrer">American Society of Human Genetics</a> (ASHG). ASHG is the primary professional membership organization for human geneticists worldwide, including 8,000 researchers, academicians, clinicians, genetic counselors, nurses, and industry professionals. This conference is one of the largest gatherings of human genetics specialists in the world and features a packed schedule of presentations, poster sessions, and exhibits during the November 2-6 event.
A few highlights from 23andMe’s conference presentations: 

<ul>
<li>With our cohort of over 3500 Parkinson’s patients and 20,000 controls, we replicate five known genetic markers for Parkinson’s disease and identify four novel associations with variants not previously known to be linked to the disease.</li>
<li>Demonstrating the power of our unique web-based approach to research, we replicate more than 100 known associations for more than 65 medical conditions, including type 2 diabetes, prostate cancer, and multiple sclerosis.</li>
<li>We report on previously unknown associations for genetic variants that influence hair color, hair curl, and yes, hair loss.</li>
<li>We report a robust new association &nbsp;between mumps susceptibility and a variant in the FUT2 &nbsp;gene which is also &nbsp;known to influence susceptibility to norovirus, the so-called Cruise Ship Virus.</li>
</ul>
We are excited to share our progress with you, and we plan to add more 23andMe reports as we move these discoveries through the scientific publication process. We are proud that our research efforts end not only in articles for the academic community, but also in the return of our findings to you, our participants, in the form of new 23andMe reports.
We believe that the results we are presenting this week demonstrate the enormous value and power of our research approach. If you have not already participated, now is a great time to <a title="survey" href="https://www.23andme.com/you/23andwe/surveys/" target="_blank" rel="noopener noreferrer">take a survey</a> or complete some research snippets. If you have already contributed, thank you, and please keep up the good work!
</div>

Kim Barnholt

23andMe at International Human Genetics Meeting

<img loading="lazy" decoding="async" class="alignright size-full wp-image-7636" title="PMWC-logo" src="https://blog-api.23andme.com/wp-content/uploads/2010/10/PMWC-logo.png" alt="" width="333" height="125" srcset="https://blogcms.23andme.com/wp-content/uploads/2010/10/PMWC-logo.png 333w, https://blogcms.23andme.com/wp-content/uploads/2010/10/PMWC-logo-300x113.png 300w" sizes="auto, (max-width: 333px) 100vw, 333px" />
A premier event in personalized medicine comes to Silicon Valley January 18-19 as the Computer History Museum in Mountain View is set to host the 2011 Personalized Medicine World Conference (PMWC). Now in its third year, this conference mixes leading-edge technologies, forward-thinking scientists, health-minded entrepreneurs, and government initiatives to accelerate developments in personalized medicine. The impressive lineup of speakers and panelists includes George Church (Professor at Harvard University and founder of the <a href="http://www.personalgenomes.org/" target="_blank" rel="noopener noreferrer">Personal Genome Project</a>, also on 23andMe&#8217;s Scientific Advisory Board) and Leroy Hood (President of the Institute for Systems Biology and keynote speaker at our Genomics and the Consumer Policy Forum last July), as well as 23andMe&#8217;s own Anne Wojcicki.
In addition to keynote presentations and panel discussions, PMWC 2011 will feature industry exhibits, a &#8220;Most Promising Company&#8221; award competition, and unparalleled networking opportunities. The two-day program includes sessions on personalized cancer medicine, emerging technologies, economics and regulation, and personal wellness.
Participants view the conference as an extremely valuable experience and a driver of change in this burgeoning field. In a press release, Dr. Hood said,
<blockquote>
&#8220;PMWC 2011 provides a unique value by bringing key decision-makers and influencers from diverse disciplines together to drive the Personalized Medicine revolution.&#8221;
</blockquote>
23andMe is excited to be taking part in this year&#8217;s event. For more information about the 2011 Personalized Medicine World Conference, visit their website.
PMWC 2011 is co-hosted by Stanford Hospital &amp; Clinics and Silicom Ventures.

The Personalized Medicine World Conference Comes to Silicon Valley in 2011

<img loading="lazy" decoding="async" class="aligncenter size-full wp-image-7521" style="margin-bottom: 10px;" title="genomesunzipped" src="https://blog-api.23andme.com/wp-content/uploads/2010/10/genomesunzipped.png" alt="" width="634" height="97" srcset="https://blogcms.23andme.com/wp-content/uploads/2010/10/genomesunzipped.png 900w, https://blogcms.23andme.com/wp-content/uploads/2010/10/genomesunzipped-300x46.png 300w, https://blogcms.23andme.com/wp-content/uploads/2010/10/genomesunzipped-768x117.png 768w, https://blogcms.23andme.com/wp-content/uploads/2010/10/genomesunzipped-880x134.png 880w" sizes="auto, (max-width: 634px) 100vw, 634px" />
A number of bloggers and researchers stand out in terms of their passion for personal genomics and in-depth coverage of this nascent industry. Many of them share 23andMe’s view that individuals should have access to their genetic information and share our vision of a future where this information has a positive impact on healthcare and people’s lives. A few months ago, some of these prominent voices banded together to form a collective blog called <a href="http://www.genomesunzipped.org/" target="_blank" rel="noopener">Genomes Unzipped</a>. Fast forward to yesterday, when they <a href="http://www.genomesunzipped.org/2010/10/our-genomes-unzipped.php" target="_blank" rel="noopener">announced</a> the true motivation behind the group’s inception: to provide informed, independent analysis of genetic testing and research illustrated through open sharing of their own genetic data.

Initially, the goal of Genomes Unzipped was to have people well-versed in genetics analyze and discuss their genetic data to help educate and inform not just consumers of genetic tests but also researchers and policy-makers interested in the scientific, social, and ethical issues surrounding this type of information. But, as Daniel MacArthur, one of the lead members, states in his announcement post:
<blockquote>“As we discussed the notion of a group of experts analysing their own genomes, one thing rapidly became clear: for maximum public benefit the analyses had to be open and reproducible, and that meant making the underlying data public. In other words, for this to work, members of the group had to be ready to spill their genetic secrets to the world.”</blockquote>
All members of Genomes Unzipped have been tested by 23andMe, and some have had additional scans performed by Counsyl and deCODEme. The members include Daniel MacArthur, a genomics researcher who blogs at <a href="http://scienceblogs.com/geneticfuture/" target="_blank" rel="noopener">Genetic Future</a>; Daniel Vorhaus of the <a href="http://www.genomicslawreport.com/" target="_blank" rel="noopener">Genomics Law Report</a>; and Caroline Wright, Head of Science at the <a href="http://www.phgfoundation.org/" target="_blank" rel="noopener">PHG Foundation</a>; among others.
Although discussion of their results and analyses are still to come, anyone can download raw genetic data and reports for these individuals for free. They have also developed a software tool for browsing genotyping data &#8212; such as that provided by 23andMe*. The browser is available on their website and allows graphical interaction with the raw data from the Genomes Unzipped members.
<img loading="lazy" decoding="async" class="aligncenter size-full wp-image-7520" style="border: 1px solid black; padding: 10px; margin-top: 10px; margin-bottom: 10px;" title="GNZ-browser" src="https://blog-api.23andme.com/wp-content/uploads/2010/10/GNZ-browser.png" alt="" width="576" height="231" srcset="https://blogcms.23andme.com/wp-content/uploads/2010/10/GNZ-browser.png 951w, https://blogcms.23andme.com/wp-content/uploads/2010/10/GNZ-browser-300x121.png 300w, https://blogcms.23andme.com/wp-content/uploads/2010/10/GNZ-browser-768x308.png 768w, https://blogcms.23andme.com/wp-content/uploads/2010/10/GNZ-browser-880x353.png 880w" sizes="auto, (max-width: 576px) 100vw, 576px" />
23andMe is not formally collaborating with Genomes Unzipped on their project and does not endorse any statements or claims made as a result of their use of the 23andMe Personal Genome Serviceâ„¢. We do believe, however, that everyone has a right to access his or her genetic information, and we are happy to see that people are empowered to learn more about their genetics, motivated to develop tools and provide a forum for understanding genetic information, and inspired to improve our knowledge of genetics as applied to individuals. Certainly, the journey on which Genomes Unzipped has embarked will be exciting and educational for participants and observers alike. We can’t wait to see where it will take us.

Researchers “Unzip” Their Genomes For The Public Good

<img loading="lazy" decoding="async" class="alignright size-full wp-image-7441" src="https://blog-api.23andme.com/wp-content/uploads/2010/10/cvr9781416569596_9781416569596.jpg" alt="" width="164" height="250">
Taken individually, the letters A, G, T, and C seem relatively harmless. However, when arranged three billion strong into a human genetic code, these letters have instilled fear of discrimination, disease risk, and a genetically engineered super race of humans (Ã&nbsp; la the 1997 film “<a href="http://www.imdb.com/title/tt0119177/" target="_blank" rel="noopener noreferrer">GATTACA</a>”). &nbsp;Once only a subject for science fiction movies, whole genome sequencing is rapidly becoming a reality for the masses. &nbsp;So, what does this mean for you? In his book The $1,000 Genome, Kevin Davies does a commendable job of answering that question.
Dr. Davies introduces us to the people and technologies that have transformed genomic sequencing from a time-consuming and billion-dollar endeavor into what is bound to become a consumer product within the next few years. The $1,000 Genome serves as an excellent guide into the rapidly evolving world of personal genomics. Kevin Davies’ educational qualifications (M.A. in biochemistry and Ph.D. in molecular genetics) combined with his professional experience (founding editor of the world’s leading genetics journal, <a href="https://www.nature.com/ng" target="_blank" rel="noopener noreferrer">Nature Genetics</a>, and author of Cracking the Genome) provide him with a depth of knowledge about the subject matter, the industry, and the people involved in the personal genomics revolution. Extensive interviews with many of the top scientists and industry leaders infuse a refreshingly human element into the story about the race to the $1,000 genome.
Although the entire book is a worthy read, I highly recommend the first and last few chapters that focus on what Davies’ terms the “personal genomics pioneers” or “23 et al.”. &nbsp;This recommendation stems in part from my own preference towards the application of personal genomics services rather than the sequencing technology (detailed in the middle chapters) as well as from an admittedly biased interest in the history of 23andMe. The 23andMe community might enjoy learning &#8212; as I did &#8212; about the co-founders’ visions for the company and the contributions by some of the early team members (one of whom is described by Davies as having “an uncanny resemblance to <a href="https://en.wikipedia.org/wiki/Ashton_Kutcher" target="_blank" rel="noopener noreferrer">Ashton Kutcher</a>”). Furthermore, for anyone who finds the various arguments surrounding an individual’s right to access his or her DNA a bit overwhelming, the latter chapters provide an expert’s perspective on the pros and cons of “genomic democratization” in the realm of health care and government institutions. Although Davies generally appears to be a proponent of consumer genomics, he also provides examples of the possible risks of widespread DNA testing in addition to the benefits.
While reading this book, I found strong parallels between Davies’ general themes and 23andMe’s overall philosophy. Both Davies and 23andMe stress the importance of “empowering the individual” and “democratizing genetics”. &nbsp;Direct-to-consumer genetic testing puts the power of knowledge into the hands of the individual, in contrast to what is often deemed the paternalistic nature of the medical establishment. In a sense, 23 et al. are to the health care industry what the Internet was to communication and commerce–both services circumvent a historically closed and hierarchical structure by enabling anyone at anytime at any place to contribute to and access information.
In addition, Davies highlights how a greater understanding of disease risk may result in an improved emphasis on preventative care rather than treatment. He states, “<a href="https://en.wikipedia.org/wiki/Leroy_Hood" target="_blank" rel="noopener noreferrer">Lee Hood</a>, who invented automated DNA sequencing in the 1980s, espouses a vision in which medicine will–indeed, must–change from its current reactive mode, in which doctors treat already sick patients, to a more rational, preventative philosophy of maintaining wellness.” &nbsp;Our goal at 23andMe is to help you take a more active role in your health by knowing your disease risk and working with your physician to make lifestyle changes accordingly. Research efforts at 23andMe aim to understand the causes underlying many complex diseases in order to improve preventative measures and treatments in the future.
Overall, The $1,000 Genome champions the innovation and progress that is possible with a multidisciplinary approach to health care. Davies goes beyond a simple informative discussion about the direct-to-consumer genetic testing industry to provide a glimpse into the ingenuity and passion of the people who are driving the change. This book will be an interesting read to all 23andMe customers who are eager to learn more about the personal genomics revolution that they have chosen to join. As Davies hints in his book, the journey has just begun!

My $0.02 about The $1,000 Genome

This week, Mary Carmichael of Newsweek is exploring the world of direct-to-consumer (DTC) genetic testing and deciding whether or not she&#8217;d like to find out about her own DNA information.
<img loading="lazy" decoding="async" class="aligncenter wp-image-6586 size-full" title="23andMe_Logo_blog" src="https://blog-api.23andme.com/wp-content/uploads/2010/05/23andMe_Logo_blog.jpg" alt="" width="350" height="349" srcset="https://blogcms.23andme.com/wp-content/uploads/2010/05/23andMe_Logo_blog.jpg 350w, https://blogcms.23andme.com/wp-content/uploads/2010/05/23andMe_Logo_blog-150x150.jpg 150w, https://blogcms.23andme.com/wp-content/uploads/2010/05/23andMe_Logo_blog-300x300.jpg 300w, https://blogcms.23andme.com/wp-content/uploads/2010/05/23andMe_Logo_blog-271x271.jpg 271w" sizes="auto, (max-width: 350px) 100vw, 350px" />
23andMe was asked to contribute a short piece on what you can–and can&#8217;t–learn from services such as ours. We were more than happy to help, as it is our firm belief that education is a critical first step toward our goal of meaningful integration of genetic information into clinical care. Below is an expanded version of <a href="http://www.newsweek.com/2010/08/03/dna-dilemma-day-two-what-can-i-learn-from-at-home-dna-tests.html" target="_blank" rel="noopener">what we wrote</a>.
If you&#8217;d like to join the conversation, leave a comment over at Newsweek, or <a href="https://twitter.com/mary_carmichael" target="_blank" rel="noopener">follow Mary on Twitter</a> and let her know what you think.
<h6>Get the Right Drug at the Right Dose</h6>
What we can tell you: Genetics can impact whether you&#8217;ll need more or less of a medication compared to most people, or whether you might be at increased risk for serious side effects.
For example, the blood thinner warfarin (Coumadin ®) can help prevent blood clots, but it can also cause excessive bleeding in people whose sensitivity to this drug is increased by two genetic variations covered by 23andMe. There are also genetic effects on clopidogrel (Plavix ®) efficacy.   Normally this drug helps prevent heart attacks by keeping blood cells from sticking together. But a genetic variation that interferes with the drug&#8217;s metabolism prevents some people from getting the full effect, putting them at increased risk for cardiovascular events.
What we can&#8217;t do: DTC genetic testing can&#8217;t replace your doctor when it comes to making decisions about how best to treat you.   There are many factors other than genetics that need to be taken into consideration.   No one should stop taking a medication or change their dosage without a doctor&#8217;s supervision.
<h6>The Future: Mutations that Could Impact Your Children</h6>
What you&#8217;ll learn: If two people are carriers of certain disease-causing mutations, each child they have together will have a 25% chance of being born with the disease.  Knowing a child has a chance of being born with one of these diseases can facilitate early intervention and improve outcomes.
One in 29 people of European descent carries a mutation that can cause cystic fibrosis.   Approximately one in five Ashkenazi Jews carries a mutation associated with a severe disease that could result in the early death of a child, such as Tay-Sachs, Canavan disease or Niemann-Pick disease type A. Sickle cell anemia occurs in about one out of 625 African Americans and one out of 1,000 Hispanic Americans.
23andMe tests for mutations associated with these and many other inherited conditions.
But remember: For almost every inherited condition, there are many, many known mutations.   Some of these are more frequent than others, and the chance of having certain mutations often varies by ethnicity.   All screening tests necessarily cover only a subset of the possible mutations for each disease.   Because of this, these tests can tell you that there is a chance that a child will be affected, but if no mutations are detected you don’t know that a child absolutely won’t be affected.   The presence of undetected mutations in each parent could still lead to a child being born with the disease.
<h6>Common Diseases — the Future of Genetics</h6>
What we know: Common DNA variations found within all of us have been linked to increased risk for things like diabetes, cancer and autoimmune conditions.Learning your genetic risk for these conditions allows you and your doctor to focus on what matters most for you.
What&#8217;s left to figure out: The genetic variations identified to date explain only a small part of a person&#8217;s risk for each disease.   Unknown genetic factors, as well as environment, are also important.   Additionally, because most research is conducted in populations with European ancestry, people from ethnic minorities get limited information from DTC genetic testing.
Through its research, 23andMe is working to improve the information that all people can get from their DNA data.   Our 23andWe surveys allow everyone to contribute to work aimed at understanding some of the most basic facets of our biology, and have already resulted in the <a href="https://blog.23andme.com/2010/06/24/plos-genetics-23andme/" target="_blank" rel="noopener">publication of a report in a peer-reviewed scientific journal</a>.   Our Parkinson&#8217;s disease and sarcoma communities are bringing people from around the world together in a participant-driven effort to make real strides in our understanding of these diseases.
We are also partnering with several groups in order to increase the diversity in our database and, in turn, the number of results we will be able to provide to all people, regardless of their ancestry.
<h6>The Fun Stuff</h6>
Some of the information hidden in your DNA is just plain cool!
Physical Traits: Is your earwax wet or dry?   Never thought about it?   Well, you will once you learn about how just one little letter in your DNA can make all the difference.   Your eye color, hair curliness, whether your sneeze upon entering bright light, and the ability to smell asparagus in your urine (ewwwwww!) are also all influenced by genetic factors.
Ancestry: Locked within your genetic code are both the story of your ancestors and the information you need to fill in your family tree.
Ancient Migrations: With state-of-the-art tools 23andMe traces maternal ancestry back tens of thousands of years with a small piece of DNA passed down from mother to child. Males can uncover their paternal ancestry through the Y chromosome that is passed down from father to son.
Global Origins: By comparing your DNA to reference populations from around the world, 23andMe can give you clues as to where each piece of your genome originated and which populations you are most similar to.
Find Relatives You Never Knew You Had: 23andMe&#8217;s Relative Finder lets you find all the other 23andMe members who match your DNA. You can browse and make contact anonymously.   Most people find over 100 &#8220;cousins,&#8221; though this varies based on ancestry.   People who have mainly European roots may find several hundred relatives. If you have Ashkenazi Jewish ancestry, you might find well over a thousand.

What DTC Genetic Testing Can–and Can’t–Tell You

<img loading="lazy" decoding="async" class="alignright size-full wp-image-6586" title="23andMe_Logo_blog" src="https://blog-api.23andme.com/wp-content/uploads/2010/05/23andMe_Logo_blog.jpg" alt="" width="237" height="236" srcset="https://blogcms.23andme.com/wp-content/uploads/2010/05/23andMe_Logo_blog.jpg 350w, https://blogcms.23andme.com/wp-content/uploads/2010/05/23andMe_Logo_blog-150x150.jpg 150w, https://blogcms.23andme.com/wp-content/uploads/2010/05/23andMe_Logo_blog-300x300.jpg 300w, https://blogcms.23andme.com/wp-content/uploads/2010/05/23andMe_Logo_blog-271x271.jpg 271w" sizes="auto, (max-width: 237px) 100vw, 237px" />
As we have previously detailed here in the Blog, 23andMe received a letter from the Committee on Energy and Commerce of the United States House of Representatives asking for details of our genetic testing services.   We received a second letter from the Committee asking for more information about the incorrect processing of a number of customer samples that we previously discussed in the Blog on June 8, 2010.
If you would like to read the letters 23andMe received from the Committee, they can be accessed as PDFs through the following links:
<ul>
<li>Letter from the Committee on Energy and Commerce of the  United States House of Representatives–May 19, 2010</li>
<li>Letter from the Committee on Energy and Commerce of the  United States House of Representatives–June, 14, 2010</li>
</ul>
23andMe is working to provide Congress with the information they have requested.   Reprinted below is the letter we sent to the Committee on June 28, 2010 in response to their inquiry about the incorrectly processed samples.

June 28, 2010

Hon. Henry A. Waxman, Chairman 
House Committee on Energy and Commerce 
2125 Rayburn House Office Building 
Washington, DC 20515-6115

Hon. Bart Stupak, Chairman 
Subcommittee on Oversight and Investigations 
2125 Rayburn House Office Building 
Washington, DC 20515-6115

Hon. Joe Barton, Ranking Member 
House Committee on Energy and Commerce 
2125 Rayburn House Office Building 
Washington, DC 20515-6115

Hon. Michael C. Burgess, Ranking Member 
Subcommittee on Oversight and Investigations 
2125 Rayburn House Office Building 
Washington, DC 20515-6115


Re: June 14, 2010 letter request to Anne Wojcicki, President, 23andMe, Inc.

Dear Chairman Waxman, Ranking Member Barton, Chairman Stupak and Ranking Member Burgess:

On June 14, 2010, you sent a letter request to Anne Wojcicki, President of 23andMe, Inc. (“23andMe” or “the Company”), seeking information related to a June 8, 2010 announcement by the Company relating to a number of customer DNA samples.   While we are in the process of producing responsive documents, the Company would like to take this opportunity to explain the incident.   At the outset, we understand that a representative of the laboratory processing and analysis company that 23andMe uses will meet with you this week and will certainly be in the best position to discuss the issues that occurred within their facility.   Our description of events at the laboratory is limited to 23andMe’s own understanding of what happened there.

I.   How 23andMe’s Collection of Customer DNA Samples and NGI’s Processing and Analysis Operate

Preliminarily, we thought it would help to provide a step-by-step explanation of how 23andMe operates with respect to the collection of customer DNA samples and their processing and analysis by the Company’s third-party laboratory vendor, the National Genetics Institute (“NGI”) a wholly owned subsidiary of the Laboratory Corporation of America.

First, customers visit the 23andMe website and purchase one of three products for personalized genetic testing.   23andMe then sends to each customer a kit to collect a DNA sample, including a vial for saliva marked with a unique barcode, from which customer DNA will be extracted and analyzed by NGI.   The customer deposits a sample of saliva in the vial and then sends it directly to NGI.   The Company uses the unique barcode on each saliva collection vial to track and distinguish each customer’s unique data while maintaining customer privacy.

NGI is a Clinical Laboratory Improvement Amendments Program-certified laboratory that

provides advanced clinical genetics testing services for blood screening, medical testing, and clinical research.   Licensed as a clinical laboratory provider by both state and federal agencies, NGI participates in a number of approved quality control programs, and holds active Biologics Licenses from the U.S. Food and Drug Administration for screening of plasma for blood borne infectious agents.   It also provides advanced genetic testing services to physicians, hospitals, and clinics and has supported numerous pharmaceutical and biotechnology companies in the clinical development of new infectious disease and oncology therapies.   (see http://www.ngi.com/services/index.asp).   We understand NGI complies with strict professional, regulatory, and corporate quality-assurance standards.   23andMe employees and consultants do not participate in the processing and analysis of data at NGI, although we rely on the data returned.


Upon receipt of the saliva samples, NGI logs them by their assigned bar codes into NGI’s system, and then processes them through “amplification,” extracting the customers’ DNA from their saliva samples.   Each customer’s DNA is then placed by pipette into an assigned slot contained on a well plate.   The well plates used by NGI for testing of 23andMe customer samples are 5”x7”, and contain 96 slots to allow for the processing of up to 96 customer DNA samples per plate.   These well plates are then inserted into Illumina-platform equipment for analysis of nearly 600,000 data points that 23andMe provides to its customers.

After NGI completes the analysis, the collected data for each sample is linked to its accompanying bar code, and NGI electronically sends the data encrypted to 23andMe through a secure FTP site.   A single electronic file contains the data from one well plate.   Upon receiving this data, 23andMe matches each barcode to the customer it belongs to, and then uploads the data from each barcode to the customer’s individual account.   Finally, 23andMe sends emails to its customers notifying them that their data are loaded and ready for viewing.

II.   Factual Background of the June 2010 Incident

Summary

In brief, the June 2010 incident was caused by the human error of one of NGI’s certified technicians accidentally and wrongly inverting one well plate, which contained 96 customer DNA samples, nine of which failed processing by 180 degrees.   This led to the Company’s receipt of incorrect results, which were then transmitted to customers.   However, 23andMe responded rapidly to the problem, advised consumers of the problem, removed the inaccurate results in less than 24 hours, and provided those impacted with their correct results within six (6) days.   While 23andMe takes the incident seriously, the Company rapidly resolved it.   Since the incident, both 23andMe and NGI have further strengthened their quality control systems to avoid any further such problems.

Detailed Account 

The aforementioned inversion of the well plate by 180 degrees caused NGI’s computer to assign DNA information to incorrect barcodes, as the slots were assigned to barcodes in the computer before plate insertion.   I note that the plate inversion could have happened in any such lab for any such tests coming from any hospital, doctor’s office, or other NGI client — it was not a problem uniquely related to 23andMe samples.   Unfortunately, NGI did not detect the error before it transmitted the erroneous electronic data file from the inverted plate to 23andMe.   The Company received the NGI-generated, faulty data and uploaded it to each customer’s individual account and emailed those customers that their data was available.   Customers received these emails between 6 and 9 p.m. on the evening of June 1.

Early in the morning of June 2, 23andMe’s Director of Engineering, Alex Khomenko, checked his email and was alerted that several 23andMe customers had apparently received inaccurate genetic reports.   For example, in at least one instance, a customer had received genetic data indicating that the customer was the wrong sex.   That same morning, Mr. Khomenko contacted the Company’s Customer Service Manager, Michelle Klucsor, who said she had received similar customer complaints via email.

To identify what happened, Mr. Khomenko ran a program covering 100% of the samples received from NGI on June 1.   This program provided the names (which the customers provided when signing up with 23andMe) and sex (which the lab identified in its DNA analysis) of these customers.   He then compared a customer’s name against the lab-identified sex of the customer.   He noticed that, in some instances, the gender of a customer’s name (for example, “Sarah”) did not match the sex (for example, “male”) contained in the lab report.   He compiled a list of all such inconsistencies.   Mr. Khomenko then reviewed the original electronic files sent from NGI on June 1, 2010 and determined that all of the inconsistencies stemmed from a single electronic file, and, thus, he concluded, from one well plate.

As Mr. Khomenko conducted his investigation, 23andMe alerted NGI of the error.   NGI also conducted its own investigation.   Around 1 pm on June 2, 2010, 23andMe concluded that the data from the single file containing 87 customer data sets contained inaccuracies and began the process of removing this data from the accompanying accounts.   During this period, 23andMe continued discussions with NGI.   At approximately 4 pm on June 2, 2010 — less than 24 hours after customers had received the incorrect data &#8212; 23andMe deleted the erroneous data from the affected customers’ databases and sent emails to each affected customer alerting them of the error.

On June 5, NGI confirmed that its investigation had concluded that the issue stemmed from an error on a single well plate.   NGI’s investigation showed that the well plate had been inverted, causing the inaccurate customer data.   NGI had reprocessed the data of all impacted customers while its investigation was ongoing.   NGI re-ran the entire plate from both the amplified DNA samples and the original saliva samples provided by the customers.   In doing so, NGI was able to confirm the accuracy of the updated data.   23andMe was able to upload correct reports into the affected customers’ accounts on June 8, 2010.

III. Steps Taken by 23andMe and NGI to Ensure No Future Errors

Since this incident, NGI has informed 23andMe that NGI has taken steps to help ensure that such errors do not recur.   Specifically, 23andMe understands that NGI has modified the physical shape of its well plates to prevent them from being inverted in the machine that conducts the analysis.   Attached please find a photograph of the old well plate and one of the newly-designed well plates that are now in use.

For its part, 23andMe has implemented improved quality-control procedures to double-check the accuracy of NGI’s returned lab results before providing them to customers.   For the period of June 8 through June 23, 23andMe cross-referenced a customer’s name (which 23andMe predicts to be either male or female based on traditional name use) with the customer’s sex information pulled from lab data.   Doing so allowed 23andMe to identify potential errors, where the gender of a customer’s name is inconsistent with lab-identified sex data for that customer.

Starting June 24, 23andMe implemented a similar quality check with additional data.   As of June 10, 2010, 23andMe has been collecting customer date of birth and sex information pursuant to requirements that NGI is following.   23andMe’s new process cross-references this customer-provided sex data with that generated by the lab data.   Potential errors will be flagged where there are inconsistencies.

We look forward to speaking with you further about this issue.   If you have any questions in the meantime, please call me at (202) 339-8523.


Sincerely,



Michael J. Madigan 
Joshua P. Galper 
Stephanie Maya Cowles

Update on 23andMe and Committee on Energy and Commerce of the United States House of Representatives

<img loading="lazy" decoding="async" class="alignright size-full wp-image-6586" title="23andMe_Logo_blog" src="https://blog-api.23andme.com/wp-content/uploads/2010/05/23andMe_Logo_blog.jpg" alt="" width="237" height="236" srcset="https://blogcms.23andme.com/wp-content/uploads/2010/05/23andMe_Logo_blog.jpg 350w, https://blogcms.23andme.com/wp-content/uploads/2010/05/23andMe_Logo_blog-150x150.jpg 150w, https://blogcms.23andme.com/wp-content/uploads/2010/05/23andMe_Logo_blog-300x300.jpg 300w, https://blogcms.23andme.com/wp-content/uploads/2010/05/23andMe_Logo_blog-271x271.jpg 271w" sizes="auto, (max-width: 237px) 100vw, 237px" />
At 23andMe, our goal is to give people the best information possible about their personal genetic data.   We believe that this goal is shared by all genetic testing providers.
You may be aware that different personal genetic testing companies, while providing completely accurate test results, may provide differing risk estimates for some diseases and conditions.   While there are valid scientific reasons for such different estimates, they might nevertheless cause confusion for some consumers and physicians.
23andMe has sent a letter to Dr. Margaret Hamburg, Commissioner of the Food and Drug Administration, and Dr. Francis Collins, Director of the National Institutes of Health, asking for their respective agencies&#8217; help in developing broadly applicable standards and guidelines to achieve consensus regarding how to provide information on genetic test results and risk estimates.   The contents of this letter are reprinted below (links to the referenced article and blog post are provided here instead of attachments):
June 24, 2010
Dr. Margaret Hamburg 
Commissioner of Food and Drugs 
Food and Drug Administration 
10903 New Hampshire Ave 
Silver Spring, MD 20993-0002
Dr. Francis Collins 
Director 
National Institutes of Health 
9000 Rockville Pike 
Bethesda, Maryland 20892
Dear Drs. Hamburg and Collins,
We are writing to ask your assistance in resolving an issue of concern to 23andMe and, likely, all genetic testing companies, whether they report their results to physicians or to consumers.   As you are aware, though results from 23andMe and other genetic testing companies are typically consistent, there have been reports of inconsistencies (Ng et al. 2009).   We believe that it is important to emphasize that different genetic testing companies can report inconsistent results even when based on tests with proven analytical validity.   The reasons for this may include: companies employ slightly different statistical models for making risk estimates; companies establish different criteria for the inclusion of associations in their reports; new associations are being discovered at a faster rate than companies’ development cycles; companies may test for an imperfectly overlapping set of genetic variants for reasons including the ability of different genotyping technologies to assay certain variants.
Although inconsistent results may have a scientifically valid basis, we recognize that they may be confusing to physicians and consumers.   However, we, as an individual company, cannot address this issue alone.   Therefore, we are writing to ask your two agencies to engage with us on this issue, to work towards solutions that can be broadly applied.   We offer the following ideas as a starting point for discussion.   An organization or group of organizations could develop:
<ul style="padding-left: 30px;">
<li>guidelines for acceptable analytical validity;</li>
</ul>
<ul style="padding-left: 30px;">
<li>standards for the positive and negative predictive value of all tests;</li>
</ul>
<ul style="padding-left: 30px;">
<li>“best practices” for companies, for instance necessitating transparency in reporting the positive and negative predictive values of their tests, so that results could be readily compared across companies.</li>
</ul>
We note that any framework developed for genetic testing companies must consider the multiple high throughput technologies on the horizon, including genome, exome and transcriptome sequencing.   For this reason, the set of ideas we present above does not include having an organization define a specific set of markers as an acceptable genetic test.
The issue of inconsistent results was one of several discussed in an <a href="https://www.nature.com/nature/journal/v461/n7265/full/461724a.html" target="_blank" rel="noopener">Opinion piece</a> by Pauline C. Ng, Sarah S. Murray, Samuel Levy and J. Craig Venter that appeared in the October 8, 2009 issue of Nature.   A joint response from 23andMe and Navigenics submitted to Nature but not published by Nature was posted on our web site on November 19, 2009.   We have attached <a href="https://blog.23andme.com/articles/23andme-navigenics-open-letter-to-nature" target="_blank" rel="noopener">our open letter to Nature, and a response from one of the authors for your consideration</a>.
Our goal is to provide the best possible information to consumers and health care practitioners.   We would appreciate the opportunity to work with you towards this goal and, more broadly, to promote innovation in personalized medicine.   We will follow up with a call to your offices.
Sincerely yours, 
Ashley Gould 
on behalf of Anne Wojcicki

23andMe Letter to Heads of FDA and NIH

<img loading="lazy" decoding="async" class="alignright size-full wp-image-6693" title="Fireworks" src="https://blog-api.23andme.com/wp-content/uploads/2010/06/iStock_000006677641XSmall.jpg" alt="" width="332" height="361" srcset="https://blogcms.23andme.com/wp-content/uploads/2010/06/iStock_000006677641XSmall.jpg 332w, https://blogcms.23andme.com/wp-content/uploads/2010/06/iStock_000006677641XSmall-276x300.jpg 276w" sizes="auto, (max-width: 332px) 100vw, 332px" />
23andMe is proud to announce the first publication out of 23andWe, our novel participant-driven research program.
Our results, which encompass replications of previous findings and newly discovered associations, appear online today in PLoS Genetics.
<a href="https://www.23andme.com/research/" target="_blank" rel="noopener">23andWe</a> is a web-based research framework designed to simultaneously facilitate the rapid recruitment of participants to many studies, thus reducing the time and money needed to make new discoveries.
&#8220;This paper announces and validates a revolutionary way of conducting scientific research,” said our President and Co-Founder, Anne Wojcicki.   “In this paper, we confirm that self-reported data from our customers has the potential to yield data of comparable quality to data gathered using traditional research methods.  We are excited about moving scientific research forward faster.&#8221;
(Check out &#8220;Sergey&#8217;s Search&#8221; in the current issue of Wired to learn how this approach is allowing us to validate genetic associations in a fraction of the time traditionally needed.   And check out this <a href="https://blog.23andme.com/articles/23andme-and-a-new-paradigm-for-research" target="_blank" rel="noopener">recent Blog post</a> to read about some of our other 23andWe successes.)
Over 9,000 people contributed data to our study of 22 separate traits. Novel SNP associations were revealed for hair curl, asparagus anosmia (the inability to detect the scent of specific asparagus metabolites in urine), the photic sneeze reflex (the tendency to sneeze when entering bright light), and freckling.
Previously identified genetic associations between nine genes and certain pigmentation-related traits (hair color, eye color, and freckling) were replicated.
23andMe chose to publish its results in PLoS Genetics because of the journal&#8217;s open-access policy. This policy allows anyone–including 23andMe customers who contributed to the research–to freely access the study. Customers will also see the results incorporated into the reports available in their online accounts.

News — Page 33