The following is a joint letter addressing the Opinion piece by Pauline C. Ng, Sarah S. Murray, Samuel Levy and J. Craig Venter that appeared in the October 8, 2009 issue of <a href="https://www.nature.com/nature/journal/v461/n7265/full/461724a.html" target="_blank" rel="noopener">Nature</a> (coverage <a href="https://www.bloomberg.com/apps/news?pid=20601124&amp;sid=ak0buXeZFk40" target="_blank" rel="noopener">here</a>, here, <a href="http://www.newscientist.com/article/dn17939-personal-genomics-firms-must-come-clean.html" target="_blank" rel="noopener">here</a>, and here).
Unfortunately, Nature could not publish the letter because of space restrictions, so 23andMe and Navigenics decided to publish the letter to our respective sites.
&#8212;
<h6>Dear Editor:</h6>
We read with interest the Opinion piece entitled “An agenda for personalized medicine” in the October 8, 2009 edition of <a href="https://www.nature.com/nature/journal/v461/n7265/full/461724a.html" target="_blank" rel="noopener">Nature</a>. Our two companies, though commercially distinct with differentiated products, would like to respond to this piece jointly to show our commitment to working together in an open, transparent fashion.
Our companies agree with most of the recommendations Ng and colleagues made.   Without doubt, genotype-based risk prediction for common, multifactorial diseases is still in its infancy.
More work must be done to standardize markers used; to better explain the contribution of genetics to common, complex diseases; and to incorporate common genetic variants into clinical practice.   Each company, however, has a few points of disagreement and/or explanation it feels important to articulate.   These points from each company follow.
<h6>Response by Navigenics:</h6>
With regard to the specific recommendations, Navigenics agrees with most of the suggestions.   For example, we agree with the authors that results showing less than average risk should not be a primary point of focus, a viewpoint that has been incorporated into our service offering in a variety of ways.  Ng et al. recommend “that DTC companies report the proportion of the genetic contribution of a disease that can be attributed to the markers used in their test…”
There are many metrics that can be used to describe the completeness/accuracy of these types of tests. However, each of them has advantages and disadvantages, and all can be misinterpreted by experts and laypersons alike.   Furthermore, the call for such information must be put in context with currently implemented non-genetic risk communication. For example, does your doctor know/communicate what percentage of the total risk of cardiac disease is contributed by your cholesterol level?   Or your family history?   Clearly, risk communication has, and will continue to be, an important area of research for the community.
We agree that associations must be replicated in other ethnicities; that prospective studies will be helpful in further assessing the validity of predictions; and that sequencing should be used when the technology becomes more affordable.
The monitoring of behavioral outcomes is another important avenue for future research, and to this end, Navigenics is collaborating with the Scripps Translational Science Institute on a 20-year longitudinal outcomes study.  Pharmacogenomic markers may also offer immediate value to individuals.
We also agree on the importance of including the same strong-effect markers, and with a few exceptions, our companies are consistent.   A standard set of markers would be valuable to the industry and personalized medicine in general, and it may be most practical for a third party to assess clinical validity.   The <a href="https://www.pnas.org/content/106/23/9362.long" target="_blank" rel="noopener">catalog of genome-wide association loci</a> sponsored by the <a href="https://www.genome.gov/26525384" target="_blank" rel="noopener">National Human Genome Research Institute</a> is an example of such a resource.   Further public-private efforts could be placed into grading the cumulative evidence supporting various marker-disease associations using, for example, the <a href="http://ije.oxfordjournals.org/cgi/content/full/37/1/120" target="_blank" rel="noopener">Venice criteria</a>.
Regarding the use of surrogate risk markers, Navigenics initially used markers in linkage disequilibrium with published SNPs (with a requirement of r2 = 1) to tag SNPs that were not on its genotyping platform. However, Navigenics now directly targets published SNPs, except for a few loci in the HLA region.
<h6>Response by 23andMe: 
</h6>
We would like to discuss two technical points about the article.   The authors presented these points in a relatively balanced manner but the subtleties have led to misinterpretations in subsequent media coverage.
The first point is that in the comparison of risk estimates, the thresholds for what Ng and colleagues consider to be “average risk” (0.95 â‰¤ relative risk â‰¤ 1.05) are somewhat restrictive.   Using this definition would be akin to telling an individual that her risk of a condition was “increased” because it was 5% more than average–technically true, but unlikely to be meaningful.
While there is no scientific consensus on what magnitude of risk equates with “meaningful” increased risk, one typically does not find relative risks less than 1.5 used today in clinical practice (e.g. family history, non-genetic biomarkers, environmental risk factors).   Thus, it would have been more appropriate to perform the consistency comparison using a wider window for “average risk”.
The second point concerns measures of genetic contribution to disease.   Ng and colleagues correctly note that for some diseases, less than half of the genetic contribution can be explained by known markers, which may lead to false negatives and false positives.   However, the metrics Ng and colleagues use to assess genetic contributionâ€•heritability and proportion of genetic contribution explainedâ€•are population-level measures that should not be applied to individual-level risk estimates, as illustrated by two examples.
Estimates of the genetic component (heritability) of Parkinson’s disease range from <a href="https://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Search&amp;db=pubmed&amp;term=15277625&amp;category=text&amp;x=0&amp;y=0" target="_blank" rel="noopener">0%</a> to <a href="http://jama.ama-assn.org/cgi/content/full/281/4/341" target="_blank" rel="noopener">27%</a>, meaning that genetics explains at most 27% of the variance in disease risk.   However, the G2019S mutation in the LRRK2 gene confers a <a href="https://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Search&amp;db=pubmed&amp;term=18539534&amp;category=text&amp;x=0&amp;y=0" target="_blank" rel="noopener">40% to 60% lifetime risk</a> of developing Parkinson’s disease, compared to <a href="http://aje.oxfordjournals.org/cgi/content/full/157/11/1015" target="_blank" rel="noopener">1% to 2% on average</a>.
The low heritability cannot–and should not–be interpreted to mean that the risk estimate of 40% to 60% is inaccurate or irrelevant, or that relative risk due to genetics must be small.   (<a href="https://www.ncbi.nlm.nih.gov/pubmed/18319743" target="_blank" rel="noopener">Visscher et al.</a> address common misconceptions about heritability in a 2009 review.)
Ng and colleagues also note that the contribution of known genetic markers to disease can be measured using percent variance explained, another population-level measure.   This statistic, too, can be misleading if applied at an individual level.   As an example, risk data for <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1377227/?tool=pubmed" target="_blank" rel="noopener">BRCA1/2 mutations and breast cancer in Ashkenazi Jews</a> can be entered into a <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2757650/?tool=pubmed" target="_blank" rel="noopener">liability threshold model</a>, which has been used to estimate percent variance explained by markers discovered in genome-wide association studies.   According to the model, the three BRCA1/2 mutations most commonly seen in Ashkenazi Jewish populations only account for about 2.5% of the variance in breast cancer risk in that population (Table 1), primarily because of the rarity of the mutations.
It would be misleading to advise a woman receiving a positive result for the 5382insC mutation in BRCA1 not to take the 81% lifetime risk of breast cancer seriously just because that mutation explains only 1.1% of the variance in breast cancer risk.   Though we agree that showing the percent variance explained by reported markers could indicate the state of genetic research on a phenotype, a low value does not necessarily mean that individual-level estimates of risk are unreliable or should be disregarded.
<table style="height: 188px;" border="1" width="551" cellspacing="0" cellpadding="0">
<tbody>
<tr>
<td width="85">
Mutation
</td>
<td width="69">
Relative risk (RR)
</td>
<td width="117">
Breast cancer risk
(RR x 12.5% average risk)
</td>
<td width="77">
Carrier frequency
</td>
<td width="85">
Percent variance explained
</td>
</tr>
<tr style="text-align: center;">
<td style="text-align: center;" width="85">BRCA1 185delAG</td>
<td width="69">
2.90
</td>
<td width="117">
36%
</td>
<td width="77">
0.0092
</td>
<td width="85">
0.6%
</td>
</tr>
<tr>
<td style="text-align: center;" width="85">BRCA1 5382insC</td>
<td width="69">
6.44
</td>
<td width="117">
81%
</td>
<td width="77">
0.0026
</td>
<td width="85">
1.1%
</td>
</tr>
<tr>
<td style="text-align: center;" width="85">BRCA2 6174delT</td>
<td width="69">
2.90
</td>
<td width="117">
36%
</td>
<td width="77">
0.0120
</td>
<td width="85">
0.8%
</td>
</tr>
<tr>
<td style="text-align: center;" width="85">All 3 mutations</td>
<td width="69">

</td>
<td width="117">

</td>
<td width="77">

</td>
<td width="85">
2.5%
</td>
</tr>
</tbody>
</table>
[Table 1.   Percent variance of breast cancer risk explained by BRCA1/2 mutations in Ashkenazi Jews, calculated using model in <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2757650/?tool=pubmed" target="_blank" rel="noopener">Raychaudhuri et al. (2008)</a>.   All data (except percent variance explained) are from <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1377227/?tool=pubmed" target="_blank" rel="noopener">Fodor et al. (1998)</a>.]
In closing, both of our companies thank Ng and colleagues for their serious consideration of genomics and personalized medicine.   We welcome further dialogue on how best to improve our offerings to the public.
Sincerely,
23andMe, Inc.
Navigenics, Inc.

23andMe Blog

23andMe Blog Team

23andMe & Navigenics’ Open Letter to Nature

<img loading="lazy" decoding="async" class="alignright size-full wp-image-3133" title="parkinsonsdisease" src="https://blog-api.23andme.com/wp-content/uploads/2009/03/parkinsonsdisease.jpg" alt="parkinsonsdisease" width="260" height="236" />PET scans showing dopamine activity in a normal brain and a Parkinson’s patient’s before and after treatment with a therapeutic implant. 
More than a million Americans have Parkinson’s disease, and another 50,000 are diagnosed each year.
Scientists know that many of Parkinson’s’s characteristic symptoms—tremors, rigid muscles, and movement problems—can be traced back to the loss of dopamine-producing brain cells. But what researchers don’t fully understand is why these cells are damaged in the first place.
<h2>Genetics and Other Factors</h2>
For most cases of Parkinson&#8217;s, the brain cell damage is probably the result of complex interactions between<a href="https://blog.23andme.com/2009/03/19/understanding-the-genetics-of-parkinsons-disease-a-work-in-progress/" target="_blank" rel="noopener noreferrer"> multiple genetic and environmental factors</a>.   Despite years of work, however, hardly any of these factors are known.   But now two research groups have identified several genetic variants associated with the risk of Parkinson&#8217;s in Asian and Caucasian populations.   Their results were published online this week in the journal Nature Genetics.
One group, led by <a href="https://dx.doi.org/10.1038/ng.485" target="_blank" rel="noopener noreferrer">Wataru Satake</a>, analyzed the DNA of 2,011 Japanese people with Parkinson&#8217;s disease and 18,381 controls.   The other group, composed of U.S. and German researchers (<a href="https://dx.doi.org/10.1038/ng.487" target="_blank" rel="noopener noreferrer">SimÃ³n-SÃ¡nchez et al.</a>), looked at the genetics of 5,074 Caucasians with Parkinson&#8217;s and 8,551 without the disease.
<h2>Common Genetic Variants</h2>
Common variations in and around two genes previously associated with rare familial forms of Parkinson&#8217;s disease, SNCA, and LRRK2, were associated with the risk for Parkinson&#8217;s in the Japanese study.   In the Caucasian study, the association with SNCA was strong, but the evidence for an association between Parkinson&#8217;s and common variation near LRRK2 was only suggestive.   Given that the association of mutations in this gene with familial forms of Parkinson&#8217;s is so strong, SimÃ³n-SÃ¡nchez et al. nevertheless think there truly is a role for SNPs near this gene in non-familial forms of the disease.
Satake et al. also found that variations in a region of the genome not previously linked to Parkinson&#8217;s disease could affect the risk for the disease.   This region of chromosome 1 contains several genes, and it is unclear which one might be involved in Parkinson&#8217;s.   Satake et al. named the region PARK16.   After comparing their data, the U.S./German group also found a link between Parkinson&#8217;s disease and the PARK16 region.
A SNP in the BST1 gene was associated with increased risk for Parkinson&#8217;s in the Japanese sample, but did not show any link to the disease in the Caucasian sample.   The risk version of this SNP, however, is found at very low levels in Caucasians.   This may have been why SimÃ³n-SÃ¡nchez et al. were unable to pick it up in their analysis.
<h2>The MAPT Gene</h2>
Finally, a SNP in the MAPT gene, which has also been associated with familial forms of Parkinson&#8217;s, was associated with disease risk in the Caucasian sample but not in the Japanese.
Work to find common genetic variations affecting the risk for Parkinson&#8217;s will no doubt continue as researchers try to identify all of the puzzle pieces relevant to this devastating disease and how they fit together.
&#8220;A further increase in the number and size of cohorts for [genomewide association studies] in [Parkinson&#8217;s disease] will likely reveal additional common genetic risk loci, and these, in turn, will improve understanding and, ultimately, treatment of this devastating disorder,&#8221; concludes SimÃ³n-SÃ¡nchez et al.
Although variations in some of the same genes were found in both the Caucasian and Japanese samples, the same SNPs often do not apply to the different populations. People looking up their own data should use the SNPs listed for the ethnicity they identify most closely with.
*Risk version is more standard version of SNP. 
**Results did not meet strict cut offs for statistical significance, but researchers suggest the associations are nonetheless real.

Genetic Variants Associated With Risk for Parkinson’s Disease

<img decoding="async" class="alignright size-full wp-image-5318" title="08D-5313-0" src="https://blog-api.23andme.com/wp-content/uploads/2009/11/arthritishands.jpg" alt="08D-5313-0" width="375" srcset="https://blogcms.23andme.com/wp-content/uploads/2009/11/arthritishands.jpg 425w, https://blogcms.23andme.com/wp-content/uploads/2009/11/arthritishands-300x199.jpg 300w" sizes="(max-width: 425px) 100vw, 425px" />
The most common type of arthritis, osteoarthritis, occurs due to accumulated wear and tear — welcome to old age! — or from repetitive movements or injury.   <a href="http://www.nlm.nih.gov/medlineplus/ency/article/000431.htm">Rheumatoid arthritis</a>, on the other hand, is caused by an autoimmune attack on the lining of the joints, resulting in stiffness, muscle aches, and general fatigue. Approximately two million people in the U.S. suffer from rheumatoid arthritis, and although women are affected more often than men, men tend to have more severe symptoms.
Research has identified a number of <a href="https://www.23andme.com/health/Rheumatoid-Arthritis/">genetic factors</a> that contribute to one’s risk of developing rheumatoid arthritis, and new studies continue to reveal more genes that seem to be involved in this complex disease. In a report published this week in <a href="https://dx.doi.org/10.1038/ng.479">Nature Genetics</a>, a team led by Soumya Raychaudhuri and Robert Plenge of Brigham and Women’s Hospital in Boston describe three new genetic associations with rheumatoid arthritis risk.
Using a computational algorithm that incorporates information from the scientific literature, Raychaudhuri and his colleagues identified 22 candidate SNPs that have a large number of connections to previously validated genetic risk factors for rheumatoid arthritis. When they tested these SNPs in a set of almost 8,000 Caucasians with rheumatoid arthritis  and 12,000 controls, seven emerged as highly significant associations. After combining this study population with that from a previous study — for a total of more than 11,000 individuals with rheumatoid arthritis and 22,000 without  — three of the variants rose to the top.
All three variants are in genes not previously linked to  rheumatoid arthritis.
These three SNPs are located near genes involved in the immune response, and, in some cases, near genetic variations that have been associated with other autoimmune disorders, such as Crohn’s disease and type 1 diabetes. Although a detailed, cohesive picture of the causes underlying rheumatoid arthritis remains elusive, each new association discovered by researchers contributes to our understanding of the biological players involved in this autoimmune disease.

Three New Genetic Variants Associated With Rheumatoid Arthritis Risk

<img loading="lazy" decoding="async" class="alignright size-full wp-image-5294" title="iStock_000001931463XSmall" src="https://blog-api.23andme.com/wp-content/uploads/2009/11/iStock_000001931463XSmall.jpg" alt="iStock_000001931463XSmall" width="318" height="211" srcset="https://blogcms.23andme.com/wp-content/uploads/2009/11/iStock_000001931463XSmall.jpg 425w, https://blogcms.23andme.com/wp-content/uploads/2009/11/iStock_000001931463XSmall-300x199.jpg 300w" sizes="auto, (max-width: 318px) 100vw, 318px" />
<a href="http://pubs.acs.org/cen/coverstory/83/8325/8325cisplatin.html" target="_blank" rel="noopener">Cisplatin</a>, a cancer chemotherapy drug first approved by the FDA in 1978, revolutionized the treatment of many types of cancer.   Despite its effectiveness, in many cases doctors are forced to reduce the drug&#8217;s dose, or abandon it altogether, due to serious side effects on patients&#8217; <a href="https://www.medscape.com/viewarticle/707849" target="_blank" rel="noopener">hearing</a>.
Between 10-25% of adults and up to 60% of children being treated with cisplatin suffer from severe, permanent hearing loss in both ears. This is particularly damaging in kids, because even mild hearing loss can negatively impact learning and social development.
Researchers have suggested that genetic variants that affect the metabolism of cisplatin might explain why some people are susceptible to drug-induced hearing loss, while other patients receiving similar doses are not.   A new report, published online this week in the journal <a href="https://dx.doi.org/10.1038/ng.478" target="_blank" rel="noopener">Nature Genetics</a>, has identified variants in two genes that appear to greatly increase the risk of cisplatin-induced hearing loss.   Although the study is a small one, if replicated these findings could one day help doctors make better decisions about how to prescribe cipslatin.
A team led by Colin Ross from the University of British Columbia analyzed the DNA of 162 children (mostly of European ancestry) treated with cisplatin, focusing their search for genetic variants associated with drug-induced hearing loss on 220 genes known to be involved in the absorption, distribution, metabolism and elimination of medications and their breakdown products.
The variants with the largest effects were found in the TPMT gene.   One of the variants was associated with increased the odds of cisplatin-induced hearing loss by 10.51 times, although this result was not statistically significant once the researchers adjusted their data to account for the number of SNPs investigated. Other variants that reduced the function of the TPMT enzyme, and have been associated with adverse reactions to a class of drugs called <a href="https://www.ncbi.nlm.nih.gov/pubmed/11966406" target="_blank" rel="noopener">thiopurines</a> that are used as chemotherapy agents and immune system suppressants.
A second SNP associated with cisplatin-induced hearing was in the COMT gene.   Having one or two Ts at this SNP increased the odds of hearing loss by 5.52 times.   This result was also not statistically significant after adjusting the data.
Other variations in the COMT gene have been associated with a variety of traits, including pain sensitivity, willingness to explore new options, <a href="https://blog.23andme.com/2009/05/01/snpwatch-genetic-variation-may-influence-heart-surgery-recovery/" target="_blank" rel="noopener">recovery from heart surgery</a>, <a href="https://blog.23andme.com/2008/08/10/snpwatch-genetic-variant-may-increase-risk-for-anxiety-disorders/" target="_blank" rel="noopener">anxiety</a>, and decreased breast cancer risk in tea drinkers.
None of the SNPs identified in this study were associated with hearing loss in children not treated with cisplatin, suggesting that their effect is specific for drug-induced hearing loss.
&#8220;These findings suggest that it may be possible identify individuals at higher risk of cisplatin otoxicity [hearing loss] based on genotype, which would improve counseling and treatment options,&#8221; the authors write.
They suggest, for example, that children with the riskier versions of the variants identified in this study could be given lower doses of cisplatin or treated instead with carboplatin, a drug that shows nearly similar cancer cure rates as cisplatin, but has less tendency to cause hearing damage.
The authors acknowledge, however, that their results will need to be replicated in independent populations before any decisions about how to use information about these variants in clinical settings can be made.   Research is also needed to understand what, if any, role these variants play in cisplatin-induced hearing loss in adult cancer patients.
Note: Recent studies by other researchers showed that variations in the <a href="https://www.ncbi.nlm.nih.gov/pubmed/17457342" target="_blank" rel="noopener">megalin </a>gene, the <a href="https://www.ncbi.nlm.nih.gov/pubmed/17228018" target="_blank" rel="noopener">GSTP1 gene and the GSTM1 gene</a> were also associated with the risk of cisplatin-induced hearing loss.   The current report from Ross et al. failed to replicate these associations.

Genetic Variations May Impact Risk of Hearing Loss in Children Receiving Common Chemotherapy Drug

<img loading="lazy" decoding="async" class="alignright size-full wp-image-5276" title="Anne Wojcicki, co-founder of 23andMe" src="https://blog-api.23andme.com/wp-content/uploads/2009/11/wojcicki1.jpg" alt="Anne Wojcicki, co-founder of 23andMe" width="130" height="170" />
The <a href="http://www.rpgeh.kaiser.org/" target="_blank" rel="noopener noreferrer">Kaiser Permanente Research Program on Genes, Environment and Health (RPGEH)</a> is an exceptional study that has the potential to transform medicine.  
As someone who proudly spent over 25 years as a patient with Kaiser, I would be excited to see my family&#8217;s medical records used for such a worthy cause.   I was disappointed, however, to learn that Kaiser will not be giving participating individuals the option to get access to the genetic data Kaiser generates in the study, as I said in my recent TEDMED talk.  
Yesterday, Cathy Schaefer, executive director of the RPGEH, commented on the <a href="http://rwjfblogs.typepad.com/pioneer/2009/11/tedmed-23andme-and-kaiser-permanentes-rpgeh.html" target="_blank" rel="noopener noreferrer">Robert Wood Johnson Foundation blog</a> that the research data will not be returned &#8220;because genetic information obtained through today&#8217;s genome-wide studies has not been designed to be useful to individuals; it is designed for use in research&#8221; (also noted by <a href="http://www.genomicslawreport.com/index.php/2009/11/03/kaiser-23andme-tedmed/" target="_blank" rel="noopener noreferrer">Genomics Law Report</a> and Genetic Future).
I strongly disagree that one&#8217;s genome is currently only useful in research and not for individual use. There are a number of highly useful genetic results that may be generated.   Individuals may learn that they are carriers for Mendelian disorders such as cystic fibrosis or sickle cell anemia.   The <a href="https://www.23andme.com/dna-health-ancestry" target="_blank" rel="noopener">genetic data</a> might reveal that an individual is at higher risk for certain diseases such as age-related macular degeneration, blood clots, Parkinson&#8217;s disease or breast cancer.   Last, the genetic data may tell an individual whether or not they are likely to respond to certain drugs, like Plavix and Coumadin.   Is it right for Kaiser to tell me what information I can or cannot have about my own body and my own genes?
I co-founded <a href="https://www.23andme.com" target="_self" rel="noopener noreferrer">23andMe</a>, a personal genetics company, to enable individuals to access their genetic information–what we believe to be a fundamental right.  
We also believe this right should extend to research participants.  
Though the RPGEH plans to inform individuals if researchers discover something that &#8220;may be important to their health&#8221;, this is not the same as an individual having their complete data in hand, and it is unlikely that researchers would continue to update 100,000 participants as genetic research progresses.
Even if genetic research is at an early stage today, having one’s genetic data will be of increasing utility as research progresses.   Individuals have a vested interest in understanding what their genetic data mean in the context of new studies.   They may examine their data through 23andMe.
The choices about what to do with that information are then with the individual, where they should be.
My husband, Sergey, learned through the 23andMe test that he is at substantially higher risk for Parkinson&#8217;s disease. That information has had a significant impact on our lives.   We eat better and we exercise more.   We are motivated to follow, participate in, and fund Parkinson&#8217;s research.   This information is important for understanding our general health and for helping us plan our lives.   Some in the medical world do not believe we should have this information.   In fact, when the Parkinson&#8217;s variant was discovered, we were dissuaded from being tested because &#8220;there is nothing to do.&#8221;   But there are things one can do, and that choice should be ours.
A growing body of evidence suggests that individuals do not suffer adverse effects from knowledge of their genetic data, and that public opinion leans strongly toward offering the return of results to research participants.  
For example, in a study of focus groups, the <a href="http://dnapolicy.org/news.release.php?action=detail&#038;pressrelease_id=116" target="_blank" rel="noopener noreferrer">Genetics &amp; Public Policy Center</a> found that “focus group participants voiced a strong desire to be able to access individual research results.”   And far from frightening people, returning genetic results could provide an incentive for future recruitment into these important studies.  
Whole-genome information would also be useful to the growing number of people interested in genealogy.
We also believe that researchers cannot know–and therefore should not dictate–what is or isn’t useful to individuals.   Even for &#8220;non-actionable&#8221; variants with severe consequences such as the ApoE e4 association with Alzheimer’s disease, research from the <a href="https://www.ncbi.nlm.nih.gov/pubmed/15757934" target="_blank" rel="noopener noreferrer">REVEAL studies</a> at Boston University showed individuals may find personal utility in having their data.   For example, they may choose to prepare their family, buy long-term care insurance, or participate in research–these are choices individuals and families have a right to make with knowledge about their own health.
Kaiser is breaking new ground with the RPGEH study but we believe they are missing a key component.  
Kaiser should afford the participants the respect they deserve by allowing them to decide for themselves whether they want to see their own genome.

Research participants have a right to their own genetic data

<img loading="lazy" decoding="async" class="alignright size-full wp-image-5263" title="cruiseship" src="https://blog-api.23andme.com/wp-content/uploads/2009/11/cruiseship.jpg" alt="cruiseship" width="350" height="260" srcset="https://blogcms.23andme.com/wp-content/uploads/2009/11/cruiseship.jpg 350w, https://blogcms.23andme.com/wp-content/uploads/2009/11/cruiseship-300x223.jpg 300w" sizes="auto, (max-width: 350px) 100vw, 350px" />
The “stomach flu” isn’t really the flu at all. It’s actually viral gastroenteritis, and its most common cause is a group of viruses called noroviruses. No matter what you call it, the illness is highly contagious and very unpleasant – symptoms include abdominal pain, vomiting, and diarrhea. In close quarters, a norovirus outbreak can quickly spread from person to person, earning the sickness the nickname “cruise ship disease.”
Norovirus is such a problem on cruise ships, in fact, that the Centers for Disease Control and Prevention (CDC) has a <a href="https://www.cdc.gov/nceh/vsp/" target="_blank" rel="noopener">Vessel Sanitation Program</a> in place to help control outbreaks. &nbsp; But the results of a new study, published in this month&#8217;s issue of the journal <a href="https://www.ncbi.nlm.nih.gov/pubmed/19814610?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum&amp;ordinalpos=2" target="_blank" rel="noopener">Clinical Infectious Diseases</a>, shows that even stricter criteria for cleanliness may be in order.
Analysis of data from 56 cruise liners evaluated between 2005 and 2008 shows that only 37% of 8,344 toilet area objects (toilet seat, flush handle or button, toilet stall inner handhold, stall inner door handle, restroom inner door handle and baby changing table surfaces) in 273 randomly selected public restrooms were cleaned on a daily basis. &nbsp; More than half of the ships had overall &#8220;thoroughness of disinfection cleaning&#8221; &nbsp; (TDC) scores less than 30%. &nbsp; Several of these low-scoring ships had nearly perfect CDC sanitation scores. &nbsp; TDC scores were substantially lower for the three ships that had a norovirus outbreak within four months of evaluation compared to those ships that did not.
Why bring this up in the Blog? &nbsp; A lucky few have less to worry about when planning a seafaring vacation: variation in the FUT2 gene renders some people resistant to the most common strain of norovirus. &nbsp; Check out the 23andMe <a href="https://www.23andme.com/health/Norovirus-Resistance/" target="_blank" rel="noopener">Norovirus Resistance Report</a> to learn more!

Ewwww: Cruise Ship Cleanliness Not What It Should Be

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New research suggests that your skills behind the wheel may be affected by your genes.
To better understand the effects of a variant in the BDNF gene on motor skills learning, Steven Cramer and colleagues at UC Irvine tested 29 subjects in a driving simulator. Their results, published in the journal Cerebral Cortex, might make you think twice about whom you go on your next road trip with.
Subjects sat in front of a screen with their hands firmly planted at &#8220;10 and 2&#8221; on a steering wheel and guided their &#8220;car&#8221; around a track, attempting to stay centered over a black line. The steering was tuned so that subjects had to begin turning before the screen actually changed.
Over the course of 15 trials, all of the study subjects got better at the driving task. But the seven people with a specific variant improved less than the others. When subjects returned to the lab four days later for a final lap, everyone had forgotten how to drive the simulator a little bit, but they did even worse.
&#8220;These people [the variant] make more errors from the get-go, and they forget more of what they learned after time away,&#8221; Cramer said in a press release.

The BDNF protein helps to regulate how nerve cells make new connections and maintain old ones. The variant, also known as the Val66Met, reduces the amount of BDNF available in the brain and has been linked to impaired learning and memory. Studies have shown that stroke victims with this variant don&#8217;t recover as well as those who lack it.
But there may be an upside: the variant seems to have a beneficial effect on cognition in people with Parkinson&#8217;s disease, Huntington&#8217;s disease, lupus and multiple sclerosis.
&#8220;It&#8217;s as if nature is trying to determine the best approach,&#8221; Cramer said. &#8220;If you want to learn a new skill or have had a stroke and need to regenerate brain cells, there&#8217;s evidence that having the variant is not good. But if you&#8217;ve got a disease that affects cognitive function, there&#8217;s evidence it can act in your favor. The variant brings a different balance between flexibility and stability.&#8221;
See <a href="https://www.wired.com/wiredscience/2009/10/genetically-bad-driving/" target="_blank" rel="noopener">Wired Science</a> for more.

The Bad Driving Gene?

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<a href="http://www.medco.com/medco/corporate/home.jsp" target="_blank" rel="noopener noreferrer">Medco Health Solutions, Inc.</a>, announced this week that it will conduct a clinical trial to assess whether clopidogrel bisulfate (Plavix ®, Bristol-Myers Squibb and Sanofi-aventis) is just as effective as the newer drug prasugrel (Effientâ„¢, Eli Lilly and Company) in people who lack a genetic variation that inhibits their metabolism of clopidogrel. This new research has important implications for both patient safety and health care costs.
Both clopidogrel and prasugrel are anti-platelet medications that reduce the ability of blood to form clots. The drugs are used to reduce the risk of a heart attack and stroke in people who have suffered from a recent cardiovascular event, and in those who have peripheral artery disease, unstable angina or a stent.
Variations in the CYP2C19 gene that prevent clopidogrel from being converted into its active form in the body have been shown to prevent patients from receiving the drug&#8217;s full benefit. People with these gene variations who are taking clopidogrel may be at a higher risk for heart attacks, strokes and death from cardiovascular causes than those whose genetics allow them to metabolize the drug.
(Prasugrel is metabolized through a different biological pathway than clopidogrel, and is not affected by CYP2C19 variants.)
Medco&#8217;s study will assess patients&#8217; rates of nonfatal heart attacks, nonfatal strokes and cardiovascular deaths after six months of treatment with either clopidogrel or prasugrel. Researchers will be looking to see if there is any difference between those patients who are taking clopidogrel, and whose genetics predict that they should be able to metabolize it–and those patients who are taking prasugrel.
&#8220;Plavix is going generic in 2011 and if found to be equally effective as Effient for patients who have a normally functioning version of the CYP2C19 gene, the study provides the evidence that would allow these patients to opt for a lower cost treatment,&#8221; said Medco&#8217;s chief medical officer Dr. Robert Epstein in a press release.
Former U.S. Secretary of Health and Human Services Michael O. Leavitt was quoted in the Medco press release as saying, &#8220;Studies like this are necessary to show how innovation can derive greater value from what we spend on health care.   A simple test can identify a drug&#8217;s ability to work for a particular patient or point them to another one that could provide a better outcome. Personalized medicine is the new frontier in making medication safer and more effective. What we learn from this study, and others like it, will save lives and money.&#8221;
Patients aren’t the only ones who would save if Medco&#8217;s research shows that the soon-to-be generic clopidogrel is an effective choice for them. An Associated Press story notes that generic drugs are more profitable for Medco than higher-priced brand name products.
Comparative effectiveness research has received a lot of attention in the United States health care debate lately.   Some worry that it will result in policies that are not in patients&#8217; best interests.
&#8220;We need to be mindful of the goal of comparative effectiveness research and not lose all that we have gained in understanding how individuals differ and how that could be factored into better diagnostics and preventive strategies,&#8221; said National Institutes of Health (NIH) director Francis Collins, speaking at a recent American Association for the Advancement of Science <a href="https://www.reuters.com/article/healthNews/idUSTRE59P4UD20091026?feedType=RSS&amp;feedName=healthNews&amp;pageNumber=1&amp;virtualBrandChannel=0" target="_blank" rel="noopener noreferrer">forum on personalized medicine</a>.
Collins recommended that genetic factors be included in comparative effectiveness research (as is the case in Medco&#8217;s study), to make sure that treatments that work for specific groups of patients are not &#8220;lost in the wash by considering everybody equivalent.&#8221;
The Genotype-Guided Comparison of Clopidogrel and Prasugrel Outcomes Study (GeCCO) is part of Medco&#8217;s “<a href="http://www.genomeweb.com/dxpgx/medcos-new-idea-pgx-program-generics-dispense-smarter-treatments-and-increase-sa" target="_blank" rel="noopener noreferrer">Genetics for Generics</a>” program and is <a href="http://clinicaltrials.gov/ct2/show/NCT00995514?term=NCT00995514&amp;rank=1" target="_blank" rel="noopener noreferrer">registered with the NIH</a>.
Related Blog Posts: 
<a href="https://blog.23andme.com/articles/more-evidence-that-genetics-can-reduce-the-efficacy-of-anti-clotting-medication-clopidogrel" target="_blank" rel="noopener noreferrer">More Evidence that Genetics Can Reduce the Efficacy of Anti-Clotting Medication Clopidogrel</a> 
<a href="https://blog.23andme.com/2008/12/23/snpwatch-genetic-variants-may-reduce-ability-of-anti-clotting-drug-clopidogrel-to-prevent-a-second-heart-attack/" target="_blank" rel="noopener noreferrer">SNPwatch: Genetic Variants May Reduce Ability of Anti-Clotting Drug Clopidogrel to Prevent a Second Heart Attack</a>

Medco to Include Genetics in Comparison of Anti-Clotting Drug Effectiveness

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There are over 50,000 people in North America who define themselves as Hutterites, though you probably have never met one. One of the main branches of the <a id="yg7o" title="Anabaptists" href="https://en.wikipedia.org/wiki/Anabaptist" target="_blank" rel="noopener">Anabaptists</a>, Hutterites live in self-sustaining communities throughout the rural northwestern United States and Canada. 
Like their sister branches, the Amish and the Mennonites, the history and culture of the Hutterites have long fascinated scholars. But there have been few forays into the genetics of this unique community – until now. In the October 21 issue of the <a href="https://www.nature.com/ejhg/journal/vaop/ncurrent/abs/ejhg2009172a.html" target="_blank" rel="noopener">European Journal of Human Genetics</a>, geneticist Irene Pichler and an international team of experts set out to unravel the genetic history of the Hutterites.
The history of the Hutterites goes back over 500 years, to a stretch of land in northernmost Italy called Tyrol. It was here that a small group of people, led by local hatmaker Jakob Hutter, formed a religious community centered on absolute pacificism and communal living. The Hutterites, as they came to be known, were part of the <a href="https://en.wikipedia.org/wiki/Radical_Reformation" target="_blank" rel="noopener">Radical Reformation</a>, which rejected the teachings of both the Roman Catholic Church and the more moderate Protestant movement. 

Due in no small part to their adherence to pacificism, the Hutterites soon became victims of persecution and expulsion. They moved several times to new settlements in central and eastern Europe. Their numbers dwindled significantly. By 1755, only 67 Hutterites were living in Transylvania. 

By 1874, the Hutterites had had enough, and over 1,200 departed Europe for the rich farmland of western North America. They settled in present-day South Dakota, setting up several colonies. Today they are living much as they were upon their arrival in both the United States and Canada. 

The Hutterites&#8217; distinct and well-documented history over the past several centuries could make for an equally unique genetic history. Would traces of their history be etched in their genes? This is exactly what Pichler and her team sought to find out. 

Pichler&#8217;s team focused on two segments of the human genome: the mitochondrial DNA and the Y chromosome. Because mitochondrial DNA (mtDNA) is passed down along the mother&#8217;s line, and the Y chromosome is passed down along the father&#8217;s line, the team could use both to paint a detailed picture of the Hutterites&#8217; genetic history. The research team also analyzed DNA from several Central European groups for comparison, as central Europe is the Hutterites&#8217; ancestral home. 

Pichler proposed that the same constant reductions in population size that continually plagued the Hutterites, must also show up in their DNA. And that is exactly what happened. Among all the Hutterite DNA samples analyzed, the authors found only 11 distinct types of mtDNA (called haplogroups), and only 10 distinct Y-chromosome haplogroups. In other words, the Hutterites&#8217; ancestral maternal and paternal lines trace back to just 21 individuals. This is an extremely small number of founders, and is further evidence that the large drops in Hutterite population size over the centuries are found in their genes. 

Pichler and her team further discovered that the haplogroups among the Hutterites are vastly different from those found among central Europeans. For example, 30 percent of Hutterites belonged to a single haplogroup called X2c1 – which is virtually absent in Europe. This shows that even while the Hutterites lived in Europe, their genetics were vastly different from their non-Hutterite neighbors. 
Centuries of isolation from the rest of Europe, followed by their massive migration to a new continent and continued isolation, have clearly defined the Hutterite people. And this study has revealed the history and genetics of this community as one of the most unique in North America.


Photo courtesy of Wikimedia Commons.

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