<img loading="lazy" decoding="async" class="aligncenter size-full wp-image-11702" title="haplogroup-I" src="https://blog-api.23andme.com/wp-content/uploads/2012/03/haplogroup-I.png" alt="" width="514" height="268" srcset="https://blogcms.23andme.com/wp-content/uploads/2012/03/haplogroup-I.png 514w, https://blogcms.23andme.com/wp-content/uploads/2012/03/haplogroup-I-300x156.png 300w" sizes="auto, (max-width: 514px) 100vw, 514px" />
<a href="http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61453-0/abstract" target="_blank" rel="noopener noreferrer">A recent study in The Lancet</a> reported that variation on the Y chromosome &#8212; haplogroup I, tagged by the SNP rs2032597 &#8212; is associated with coronary artery disease (CAD) in British men, with an odds ratio of 1.56. This finding stands out for several reasons. For one thing, the effect is substantially larger than any other reported genetic associations with CAD. Furthermore, it is rare to hear about functional effects of Y chromosome variation &#8212; at least partly because the Y chromosome is small and contains very few genes. The finding also invites special attention for some of the same reasons that make the Y chromosome interesting for population genetics. Here, we discuss the special properties of the Y chromosome and their implications for association studies, our concerns about the evidence the authors use to support their finding, and observations from the 23andMe database for haplogroup I and heart disease.
<h6>Why the Y is problematic</h6>
Most of the Y chromosome is not subject to recombination (the shuffling of maternal and paternal DNA that creates the unique genetic material passed down through sperm and egg) and is inherited intact from father to son. A consequence of this is that genetic variation on the Y chromosome is strongly associated with genetic ancestry. That doesn&#8217;t necessarily mean that genetic variation on the Y can&#8217;t also be functional, but it complicates functional analyses because it can be especially difficult to distinguish between ancestry effects and effects that are directly due to a particular Y chromosome variant. The lack of recombination also means that variants that are very far apart on the Y chromosome can still be strongly correlated, so it is also very difficult to use an association on the Y chromosome to identify a particular region as functionally important: the causal variant could be almost anywhere on the chromosome.
<h6>How strong is the evidence?</h6>
In The Lancet study, the authors carefully checked for alternative explanations for the association between haplogroup I and CAD. They looked for differences in conventional cardiovascular disease risk factors &#8212; both clinical biomarkers like blood pressure, BMI, and HDL, and lifestyle factors like smoking, alcohol consumption, and education &#8212; between haplogroup I and other haplogroups. None of these explained the association between haplogroup I and coronary artery disease. The authors also showed that the presence of haplogroup I did not correlate with the most significant dimensions of genetic ancestry within the study participants. This is a little surprising because haplogroup I is differentially distributed across Europe on a larger scale: it has a higher prevalence in Scandinavia and a lower prevalence in Southern Europe. Of course, it is possible that this gradient is not present in the smaller population of British men.
The trouble with candidate gene studies Candidate gene association studies (studies looking at one or a few genes as opposed to studies looking at variation across the entire genome) have a long and somewhat sordid history, largely because we tend to misjudge our ability to choose hypotheses that have a good likelihood of being true. If we choose a SNP at random and hypothesize that it might be associated with CAD, it would probably be better to use the genome-wide threshold for statistical significance (p-value &lt; 5 x 10-8) to evaluate the results, rather than, say, P &lt; 0.05 based on the fact that we have done just a single statistical test. If we&#8217;ve used a lot of prior knowledge to choose this one SNP, then maybe we could argue for using a more lenient standard. But it is very hard to decide how much prior knowledge is &#8220;worth&#8221; in this context.
What about the statistical evidence in favor of the haplogroup I association? In the target population of British men, more than 90% of individuals have either haplogroup I or another paternal haplogroup, R1b1b2. One could thus argue that the authors are effectively performing just a single statistical test comparing these two groups. On that basis, their statistical results (p-values of 0.004 in their initial study set, 0.012 in their replication set, and 0.0002 overall), seem convincing. However, it could be argued that the odds were stacked against their initial hypothesis that Y chromosome variation might be associated with CAD. The reported result would not meet criteria for significance in a genome wide association study (typically, p-values &lt; 5 x 10-8), so a lot depends on the credibility of this initial hypothesis.
The authors suggest that their hypothesis was motivated by the observation that CAD is more common in men than women but this fact is not convincing by itself. Physical differences between men and women are largely determined by the presence or absence of the Y chromosome, but that does not necessarily mean that specific variations on the Y chromosome affect traits or risk for disease among men. (It is much more likely that variations in many other parts of the genome that are functionally involved in those traits account for those differences.) The authors also cite work on animal models, as well as a few studies in humans suggesting that Y chromosome variants may affect cardiovascular phenotypes. However, the authors did not test the specific variants or phenotypes implicated in those studies.
<h6>Findings in the 23andMe community</h6>
We investigated whether the tag SNP for haplogroup I &#8212; the C version of rs2032597 &#8212; was associated with cardiovascular phenotypes in men with European ancestry from the 23andMe community using four traits: self-reported coronary artery disease, heart attack, high blood pressure, and high cholesterol. The following table shows results of association tests for these phenotypes. We see no significant association between rs2032597 and any cardiovascular phenotype, and can easily exclude values as large as the odds ratio of 1.56 reported by the authors of the Lancet study.
<div style="border: 1px solid #ccc; padding: 10px; margin-top: 10px; margin-bottom: 10px;">
Table 1. Association results for rs2032597 and heart disease phenotypes
<table style="font-family: 'Courier New'; font-size: 13px;" cellspacing="10">
<tbody>
<tr>
<td></td>
<td># cases</td>
<td># controls</td>
<td>p-value</td>
<td>Effect</td>
<td>95% CI</td>
</tr>
<tr>
<td>Coronary artery disease</td>
<td>1014</td>
<td>20120</td>
<td>0.92</td>
<td>1.009</td>
<td>[0.845,1.206]</td>
</tr>
<tr>
<td>Heart attack</td>
<td>486</td>
<td>22498</td>
<td>0.31</td>
<td>0.881</td>
<td>[0.687,1.130]</td>
</tr>
<tr>
<td>High blood pressure</td>
<td>5230</td>
<td>15797</td>
<td>0.34</td>
<td>0.958</td>
<td>[0.878,1.046]</td>
</tr>
<tr>
<td>High cholesterol</td>
<td>7970</td>
<td>15030</td>
<td>0.84</td>
<td>1.008</td>
<td>[0.932,1.090]</td>
</tr>
</tbody>
</table>
</div>
In contrast, we replicate the association for rs4977574, which is the variant (located on chromosome 9) most strongly associated with CAD in a recent <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3119261/" target="_blank" rel="noopener noreferrer">large-scale meta-analysis</a>. In this case, results from the 23andMe database match the reported odds ratio of 1.3, suggesting that self-reported data from 23andMe members is sufficient for detecting true associations.
<div style="border: 1px solid #ccc; padding: 10px; margin-top: 10px; margin-bottom: 10px;">
Table 2. Association between rs4977574 and heart disease phenotypes
<table style="font-family: 'Courier New'; font-size: 13px;" cellspacing="10">
<tbody>
<tr>
<td></td>
<td># cases</td>
<td># controls</td>
<td>p-value</td>
<td>Effect</td>
<td>95% CI</td>
</tr>
<tr>
<td>Coronary artery disease</td>
<td>1014</td>
<td>20120</td>
<td>2.7E-08</td>
<td>1.312</td>
<td>[1.192,1.444]</td>
</tr>
<tr>
<td>Heart attack</td>
<td>486</td>
<td>22498</td>
<td>3.9E-05</td>
<td>1.318</td>
<td>[1.155,1.503]</td>
</tr>
<tr>
<td>High blood pressure</td>
<td>5230</td>
<td>15797</td>
<td>0.0091</td>
<td>1.065</td>
<td>[1.016,1.117]</td>
</tr>
<tr>
<td>High cholesterol</td>
<td>7970</td>
<td>15030</td>
<td>0.18</td>
<td>1.029</td>
<td>[0.987,1.073]</td>
</tr>
</tbody>
</table>
</div>
<h6>Concluding thoughts</h6>
What might explain the failure to replicate The Lancet finding in the 23andMe cohort? One possibility is that it is simply a false positive, and the apparent replication in the original study was just luck. Another possibility is that the association is real but restricted to the original study population of British men. That is, it might replicate in a new study of British men, but might not generalize well. Distinguishing between these possibilities will probably require additional studies, since it is very difficult to &#8220;prove a negative&#8221; and establish that a hypothetical association does not exist. The authors suggest that their study is the first to evaluate association between Y chromosome haplogroups and CAD. However, rs2032597 is present on recent Illumina SNP arrays used for GWAS, so data for this variant should exist in other large studies of CAD. Thus, it should be possible to quickly test many cohorts for this association, even if the Y chromosome data has not been previously analyzed.

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Haplogroup I Likely Not Linked to Heart Disease

<img loading="lazy" decoding="async" class="alignright size-medium wp-image-9941" title="exome_banner" src="https://blog-api.23andme.com/wp-content/uploads/2011/10/exome_banner-300x151.png" alt="" width="300" height="151" srcset="https://blogcms.23andme.com/wp-content/uploads/2011/10/exome_banner-300x151.png 300w, https://blogcms.23andme.com/wp-content/uploads/2011/10/exome_banner.png 419w" sizes="auto, (max-width: 300px) 100vw, 300px" />
Six months ago, we announced our Exome 80X pilot project. At 23andMe, we’ve carefully followed every advance in sequencing technologies and read every paper comparing them, waiting for the opportunity to offer a meaningful and affordable option to the consumer market. While other (expensive) offerings have been available for some time, we’ve seen that consumers have been waiting for this opportunity, too.
Today, we delivered our first batch of exome data to the earliest project participants. There are many more still being sequenced and processed, but this is an exciting milestone in the development of our platform. We’re proud to share this moment with our pilot customers, many of whom are experts in their own right, and hope to learn as much in the coming months from their personal experiences with the data as we are learning from ours.
As more participants get their data, we encourage everyone* (exome or not) to join the discussion in our exome community.
* You must be a 23andMe customer to participate in the 23andMe Community forums.

Exomes — The First of Many!

In the lead up to this week’s arguments at the Supreme Court over the health care reform law, 23andMe got the opinion of two doctors on what’s ailing the country’s medical system.
On separate visits we heard from<a href="http://www.venrock.com/team/#/team/?item=99"> Bob Kocher</a>, an MD and partner at<a href="http://www.venrock.com/?home=1"> Venrock</a> who previously served as a special assistant to the president for Healthcare and Economic Policy and was instrumental in writing the reform law. A few weeks after hearing from Kocher we heard from<a href="http://xnet.kp.org/newscenter/aboutkp/bios/california/pearl.html"> Robert Pearl</a>, also an MD and the Executive Director and CEO of<a href="https://members.kaiserpermanente.org/kpweb/aboutus.do"> The Kaiser Permanente Medical Group</a>. Under Pearl’s leadership Kaiser has been singled out as an example of how to deliver quality affordable health.
<img loading="lazy" decoding="async" class="alignright size-medium wp-image-11984" title="robert_pearl" src="https://blog-api.23andme.com/wp-content/uploads/2012/03/robert_pearl1-300x290.jpg" alt="" width="300" height="290" srcset="https://blogcms.23andme.com/wp-content/uploads/2012/03/robert_pearl1-300x290.jpg 300w, https://blogcms.23andme.com/wp-content/uploads/2012/03/robert_pearl1.jpg 488w" sizes="auto, (max-width: 300px) 100vw, 300px" />Robert Pearl, MD
While Kocher’s and Pearl’s opinions on the law and whether the court will uphold it diverged on some points, both men offered a pretty grim diagnosis if some sort of reform doesn’t go forward. Spending on health care continues to grow more rapidly than the economy as a whole. We now spend about 18 percent of our GDP on health care or   – a larger share than what we spend on manufacturing or retail trade. Back in the early 1960s health care costs were only about 4 percent of GDP. According to Pearl, the rapidly growing costs are on course to cripple the economy.
The irony about all this spending is that while we pay out far more than any other country in the world and more than twice the average for industrialized countries, our<a href="http://blogs.ngm.com/.a/6a00e00982269188330120a7a46406970b-popup"> outcomes are worse</a>. We have lower life expectancy and higher infant mortality rates than countries that spend far less.
Under the current system there aren’t incentives for preventing diseases. All the upside is in treatment or interventions and this drives costs up.
“People have a hard time understanding that we are able to spend less and improve quality,” said Pearl.
He touted Kaiser – the largest medical group in the nation – as a model for better care at less cost.
“If every American got the same care (as they do at Kaiser) there would be 200,000 fewer strokes each year, 75,000 people wouldn’t die of cancer and the mortality rate of AIDS/HIV would be halved; sepsis in hospitals would diminish by 40 percent,” Pearl said.
Some of this is done through better use of data, integrating treatment and preventative care and effectively using technology. He pointed out that in many ways medical care is still a cottage industry in America with doctors providing “piecemeal” services isolated from each other. And he said the system is largely out of touch with the economic efficiencies and technologies we see in other sectors, like banking.  He foresees simple fixes such as the widespread use of electronic records similar to the system used by Kaiser, as well as video-links for some types of doctors visits and the use of more email exchanges between doctors and patients. All these can reduce costs and improve efficiency, he said.
Much of this is in line with Kocher’s prescription for reform.
<img loading="lazy" decoding="async" class="alignright size-medium wp-image-11979" title="Bob Kocher - Venrock" src="https://blog-api.23andme.com/wp-content/uploads/2012/03/Bob-Kocher-MD-300x300.jpg" alt="" width="300" height="300" srcset="https://blogcms.23andme.com/wp-content/uploads/2012/03/Bob-Kocher-MD-300x300.jpg 300w, https://blogcms.23andme.com/wp-content/uploads/2012/03/Bob-Kocher-MD-150x150.jpg 150w, https://blogcms.23andme.com/wp-content/uploads/2012/03/Bob-Kocher-MD-768x768.jpg 768w, https://blogcms.23andme.com/wp-content/uploads/2012/03/Bob-Kocher-MD-1024x1024.jpg 1024w, https://blogcms.23andme.com/wp-content/uploads/2012/03/Bob-Kocher-MD-880x880.jpg 880w, https://blogcms.23andme.com/wp-content/uploads/2012/03/Bob-Kocher-MD-1180x1180.jpg 1180w, https://blogcms.23andme.com/wp-content/uploads/2012/03/Bob-Kocher-MD-271x271.jpg 271w, https://blogcms.23andme.com/wp-content/uploads/2012/03/Bob-Kocher-MD-372x372.jpg 372w, https://blogcms.23andme.com/wp-content/uploads/2012/03/Bob-Kocher-MD-574x574.jpg 574w, https://blogcms.23andme.com/wp-content/uploads/2012/03/Bob-Kocher-MD-980x980.jpg 980w, https://blogcms.23andme.com/wp-content/uploads/2012/03/Bob-Kocher-MD.jpg 1395w" sizes="auto, (max-width: 300px) 100vw, 300px" />Bob Kocher, MD
Back in 2009, Kocher and several others authored a report for the Brookings Institute, called “Bending the Cost Curve,” that outlined in detail several strategies for reducing the growth of health care costs. Many of these ideas were incorporated into the health care reform bill.
He outlined for us some of the things he felt were key components of those strategies, foremost of which was moving away from paying by treatments toward a system that bundled payments. For example instead of compensating a hospital for all the different treatments they delivered to a diabetes patient in a year, the hospital would be paid one lump sum for treating everything related to that patient’s care in a year while meeting certain quality metrics.
Both Kocher and Pearl also talked about giving patients access to more information to involve them in their own health decisions and empower them to make choices. Kocher mentioned that giving people more information about the costs and performance of doctors and hospitals empowers them to be better consumers. They’ll know which doctors and hospitals have better outcomes and this will help them make smarter decisions when choosing where they spend their health care dollars. This is also the premise behind the company Castlight Health, where Kocher is on the board of directors.
Both Kocher and Pearl believe that genetics tests like 23andMe’s will play a role in making health care more personal and they believe that the tests will become increasingly more commonplace. But, as Pearl said, there is a long delay in the adoption of new technology within the health care industry. There is also a lot of negative inertia within the system in which the rewards are for treatment not for prevention.
23andMe CEO and co-founder Anne Wojcicki<a href="https://www.huffingtonpost.com/anne-wojcicki/secret-code-dna_b_1187141.html"> recently wrote</a> about this explaining:
“If I develop type 2 diabetes, the whole healthcare system knows how to deal with it, treat and profit from it. But if I discover I am at high risk for type 2 diabetes, I change my diet and exercise patterns and successfully prevent it, no one profits but me. We believe that engaging people in their own health care by giving people access to their genetic information and informing them of how to prevent disease can help.”
While all the attention this week is on the legal questions being argued in front of the Supreme Court, this broader question about how best to lower costs, improve quality and empower people in their own health care isn&#8217;t going to go away any time soon.

A photo of a doctor showing a patient information on a digital tablet.

Spending Less and Improving Health Care

<img loading="lazy" decoding="async" class="alignnone wp-image-11835" src="https://blog-api.23andme.com/wp-content/uploads/2012/03/Shar-Pei-200x300.jpg" alt="" width="200" height="300" srcset="https://blogcms.23andme.com/wp-content/uploads/2012/03/Shar-Pei-200x300.jpg 200w, https://blogcms.23andme.com/wp-content/uploads/2012/03/Shar-Pei.jpg 283w" sizes="auto, (max-width: 200px) 100vw, 200px" />
<div style="width: 350px; background-color: #eeeeee; padding: 15px; margin-left: 10px; text-align: center; padding-bottom: 20px; font-size: 14pt;"><a href="http://www.nationalpuppyday.com/" target="_" rel="noopener">March 23rd is National Puppy Day!</a></div>
How did the Shar-Pei get his wrinkly skin? The question sounds like the beginning of one of Kipling’s “Just So” stories, but this and other questions were the subject of a recent genetics study. What gives some breeds their Lilliputian legs and others their lengthy limbs? Why do some breeds have docile dispositions and others tenacious temperaments?
The answers may lie in their doggy genes.
This study is not the first in canine genetics, and several genes have already been associated with size (IGFI), coat type (RSPO2, FGF5, KRT71), coat color (MITF, CBD103), short limbs (FGF4), snub noses (THBS2), and wrinkly skin (HAS2).
This new <a href="https://www.ncbi.nlm.nih.gov/pubmed/22022279" target="_" rel="noopener">study</a>, however, is different because the researchers developed a new DNA chip that analyzes the canine genome in higher resolution, and they used it to focus on behavioural traits as well as physical traits Altogether, the international group of scientists led by Matthew Webster &#8212; spanning France, Sweden, Finland, Spain, Denmark, and the United States &#8212; looked at the genetics of 509 dogs from 46 different breeds.

Although dogs were domesticated from wolves over 15,000 years ago, only in the last few centuries did dogs fan out into the distinct breeds we have today. Normally evolution is propelled by survival fitness; animals that survive better reproduce better, passing on their genetics and unique traits. &nbsp;In the case of dogs, however, the selective pressure was artificial. &nbsp;
Instead of fitness being based on increased survival in the wild, dogs were bred for size, disposition, and other traits that were deemed desirable by their owners.
<div style="float: left; width: 330px; height: 585px; border: 1px solid grey; padding-right: 10px; margin-right: 15px;">
<img loading="lazy" decoding="async" class=" wp-image-11834" src="https://blog-api.23andme.com/wp-content/uploads/2012/03/breedTree-300x291.gif" alt="" width="300" height="291" srcset="https://blogcms.23andme.com/wp-content/uploads/2012/03/breedTree-300x291.gif 300w, https://blogcms.23andme.com/wp-content/uploads/2012/03/breedTree-768x746.gif 768w, https://blogcms.23andme.com/wp-content/uploads/2012/03/breedTree-1024x994.gif 1024w, https://blogcms.23andme.com/wp-content/uploads/2012/03/breedTree-880x854.gif 880w" sizes="auto, (max-width: 300px) 100vw, 300px" />Figure 1 of the 2011 PLoS Genetics paper clusters 509 dogs based on their genetic similarity. In this figure, dogs that are genetically similar to each other are grouped together, and, not surprisingly, this grouping corresponds quite well with breed (dogs of the same breed are grouped together). Some breeds do cluster together (for instance, all the retrievers are clustered together, as are the all the spaniels), but the relatively long branches connecting dogs within the same breed and the relatively short branches connecting the different breeds together is consistent with breeds which originated from a common dog gene pool long ago and have remained quite distinct. Image from <a>Vaysse A, et al. PLoS Genet. (2011) vol. 7 iss. 10 pp. e1002316</a>.
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This study by Webster and his colleagues suggests that the artificial evolution of dogs into their distinct breeds was very fast and very directed: even breeds within typically recognized subgroups (e.g. retrievers, spaniels, setters, and terriers) diverged from each other quite early. For example, Golden Retrievers and Labrador Retrievers are now quite genetically distinct after only a few centuries of breeding. A striking figure from their paper illustrates this concept.
Webster’s team further showed that some well-recognized dog traits can be traced to specific genetic variations, even across breeds.
For instance, they found a novel association between a region on chromosome 1 and curly tails across several breeds. In addition, ear morphology (pricked ears vs. dropped ears), size, and “boldness” of &nbsp;disposition (as measured by the Swedish Kennel Club) are all associated with genetic variation within one section of chromosome 10. They also found that the boldness trait was associated with the other two traits: all of the small, pricked-eared breeds studied were categorized as “bold” and all of the large, drop-eared breeds were categorized as “non-bold,” except for the Bernese Mountain Dog. &nbsp;
The researchers suggest that breeders may have optimized for certain ear morphologies, sizes, and/or degrees of boldness, thus putting selective pressure on this region of chromosome 10.
In addition to traits selected for in multiple breeds, the study also addressed a handful of more unusual traits that occur in only one or two breeds. Confirming earlier findings, Webster’s results suggest that the real story behind the Shar-Pei’s wrinkled skin may lie with mutations near the HAS2 gene on chromosome 13.
Likewise, their findings support the previously held hypothesis that the Dachshund’s short limbs may be due to mutations near the FGF4 gene on chromosome 18. These genetic regions are quite distinct from the corresponding regions in other breeds, representing a signal for active selection.
The delightfully friendly disposition of the Golden Retriever, the comically short gait of the Dachshund, and the adorably furrowed hide of the Shar-Pei are no accident. &nbsp;
These and the many other charming (and sometimes useful) attributes exhibited by modern breeds are the result of strong selective pressures, as this work illustrates. Dogs perfectly suit humans because they were bred to perfectly suit us. Of course the dog is “man’s best friend” &#8212; with such a pedigree, how could it be anything else?

How Did the Shar-Pei Get His Wrinkly Skin?

Clinical trials are often conducted at major hospitals and medical centers.    As you can imagine, it can be expensive to use hospital resources and take a large amount of  doctors’ and nurses’ time.
<img loading="lazy" decoding="async" class="alignright wp-image-11765 size-full" title="Togethermakedifference" src="http://35.88.189.111/wp-content/uploads/2012/03/Togethermakedifference.jpg" alt="" width="369" height="382" srcset="https://blogcms.23andme.com/wp-content/uploads/2012/03/Togethermakedifference.jpg 369w, https://blogcms.23andme.com/wp-content/uploads/2012/03/Togethermakedifference-290x300.jpg 290w" sizes="auto, (max-width: 369px) 100vw, 369px" />
It can also be difficult to find people to participate in clinical trials.    For those who do participate, it can be very time consuming.    For example if a person does not live  near the hospital where the trial is being conducted, the travel back and forth to doctor appointments alone can be a hardship.
We believe that people deserve better.    When we started 23andMe, our dream was to change how we approach clinical trials.    We want to make it less expensive, less  time consuming and ultimately speed the pace of meaningful research and discoveries.
Today — we feel like things are starting to change.    This week we announced that 23andMe and Genentech launched <a href="https://www.23andme.com/invite-study/">an online breast cancer study</a> to learn more about  how genes influence a person&#8217;s response to bevacizumab (also known as Avastin ®) in the treatment of metastatic breast cancer.
We are looking for 1,000 women with metastatic breast cancer who took bevacizumab in 2010 or 2011.  Normally this kind of clinical trial would take years to do.  We believe that by  leveraging the web and modern technology we can do this study much faster, more effectively and for less money.
We salute Genentech for seizing the opportunity to rethink the approach to researching medicines with this first-of-its-kind clinical trial.  Technology has improved our  lives and will hopefully soon improve all our health care.
Bevacizumab is not approved by the FDA for the treatment of breast cancer. The InVite study is for research purposes only.
For more information on bevacizumab visit  <a href="http://www.gene.com/gene/products/information/oncology/avastin" target="_blank" rel="noopener noreferrer">http://www.gene.com/gene/products/information/oncology/avastin</a>. For more information on 23andMe&#8217;s and Genentech&#8217;s online metastatic breast cancer study visit <a href="https://www.23andme.com/invite-study/#">https://www.23andme.com/invite-study/#</a>.
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Breast Cancer Research Goes Online

<img loading="lazy" decoding="async" class="wp-image-11716 size-full alignright" src="http://35.88.189.111/wp-content/uploads/2012/01/Q1-2012-Health-Watch-Word-Cloud.png" alt="" width="1496" height="692" srcset="https://blogcms.23andme.com/wp-content/uploads/2012/01/Q1-2012-Health-Watch-Word-Cloud.png 1496w, https://blogcms.23andme.com/wp-content/uploads/2012/01/Q1-2012-Health-Watch-Word-Cloud-300x139.png 300w, https://blogcms.23andme.com/wp-content/uploads/2012/01/Q1-2012-Health-Watch-Word-Cloud-768x355.png 768w, https://blogcms.23andme.com/wp-content/uploads/2012/01/Q1-2012-Health-Watch-Word-Cloud-1024x474.png 1024w, https://blogcms.23andme.com/wp-content/uploads/2012/01/Q1-2012-Health-Watch-Word-Cloud-880x407.png 880w, https://blogcms.23andme.com/wp-content/uploads/2012/01/Q1-2012-Health-Watch-Word-Cloud-1180x546.png 1180w" sizes="auto, (max-width: 1496px) 100vw, 1496px" />
Like many people around the world, the health content team at 23andMe rang in 2012 with resolutions of staying healthy and it seemed fitting to delve into the genetics underlying response to diet and exercise, eating behavior and cholesterol levels. As we eased in to the new year, we segued into reproduction, updating our existing reports on male infertility and gestational diabetes, and we also recently added new genetic associations for tuberculosis susceptibility, Hodgkin lymphoma, and atopic dermatitis.
In the end of February we paid tribute to rare diseases by celebrating <a href="../2012/02/29/did-you-know-its-not-so-rare-to-have-a-rare-disease/" target="_blank" rel="noopener">Rare Disease Day</a> and putting out new reports for <a href="https://www.23andme.com/sarcoma/" target="_blank" rel="noopener">sarcoma</a> and <a href="https://www.23andme.com/mpn/" target="_blank" rel="noopener">myeloproliferative neoplasms (MPN)</a> –  rare cancers that we are particularly passionate about as evidenced by our <a href="../2012/02/27/weve-come-a-long-long-way-together-but-were-not-there-yet/" target="_blank" rel="noopener">innovative research efforts</a> for these conditions.
Read more about some of our new and updated reports…
<h6>Tying genetics to diet and exercise</h6>
Does exercise help you lose weight or does it barely seem to make a difference? Have you ever wondered why some people who eat a lot of fatty foods don’t gain weight while others seem to pack on the pounds? Our Response to Exercise and Response to Diet reports may provide insight into the genetics underlying these complex topics that are already known to be strongly influenced by behavior and environment. Similarly, if you tend to reach for second helpings, our report on eating behavior may also shed some light!
<h6>Insight into your cholesterol</h6>
Have you ever wondered why your LDL cholesterol level is naturally low or why it seems to stay high despite your best efforts to lower it? Towards the end of January we added a new report for LDL cholesterol – the “bad” cholesterol that is associated with heart disease – and updated our report on HDL cholesterol, which is the “good” cholesterol that is considered protective against heart disease. These reports may offer some clues for you,  but it’s important to keep in mind that the genetic landscape of cholesterol levels is highly complex and that lifestyle also plays a big role.
<h6>Genetic findings on reproductive health in Asians!</h6>
Sexual reproduction is what keeps the human species going, but from getting pregnant to having a healthy child, it doesn’t always work like a well-oiled machine. Approximately 15% of couples experience difficulties getting pregnant and <a href="../2012/02/06/snpwatch-genetic-variants-linked-to-male-infertility-in-asians/" target="_blank" rel="noopener">about half of these cases</a> are due to male infertility. We’ve updated our Male Infertility report to include genetic variants that influence sperm count in Asian men. In February we also added new findings for Asian women to our report on gestational diabetes, a pregnancy complication with symptoms similar to type 2 diabetes that affects about 3-5% of pregnant women.
<h6>Revving up reports for rare diseases</h6>
In the United States, a disease is defined as “rare” if it affects<a href="http://rarediseaseday.us/about/" target="_blank" rel="noopener"> fewer than 200,000 individuals</a>, or roughly one in 1500. Sarcoma and myeloproliferative neoplasms (MPN) fall into this category and in early March we added new reports for both of these rare cancers. Although these reports are considered “preliminary research” findings, mainly because they were generated with relatively small study groups, they are still exciting progress in research on these rare disorders.
23andMe customers can find more details on these and other conditions in their accounts. Not a member? <a href="https://www.23andme.com/store" target="_blank" rel="noopener">Visit our store</a>, or set up a<a href="https://www.23andme.com/user/signup/" target="_blank" rel="noopener"> free trial account</a> to browse these and other reports.

Health Watch: New Year’s Resolutions, Reproduction and Rare Diseases

On a recent visit to 23andMe George Demetri –a physician and scientist who is an unpaid advisor to our<a href="https://www.23andme.com/sarcoma/"> Sarcoma research initiative</a> – sat down for a short interview after talking to our team. 
Demetri, who is also the director of the Dana-Farber Center for Sarcoma and Bone Oncology, said he has a lot to be optimistic about in the study of sarcoma. Individually, these are rare kinds of cancers that affect bone, cartilage, muscle, and other soft connective tissue in the body.
<img loading="lazy" decoding="async" class="alignright wp-image-11542 size-medium" title="george&amp;Anne" src="http://35.88.189.111/wp-content/uploads/2012/03/georgeAnne-300x194.jpg" alt="" width="300" height="194" srcset="https://blogcms.23andme.com/wp-content/uploads/2012/03/georgeAnne-300x194.jpg 300w, https://blogcms.23andme.com/wp-content/uploads/2012/03/georgeAnne-768x496.jpg 768w, https://blogcms.23andme.com/wp-content/uploads/2012/03/georgeAnne-1024x661.jpg 1024w, https://blogcms.23andme.com/wp-content/uploads/2012/03/georgeAnne-880x568.jpg 880w, https://blogcms.23andme.com/wp-content/uploads/2012/03/georgeAnne-1180x762.jpg 1180w" sizes="auto, (max-width: 300px) 100vw, 300px" />Dr. George Demetri and 23andMe&#8217;s CEO Anne Wojcicki
Genetics often triggers different sarcomas, but, as with most cancers, there seldom is a single cause. This makes treating sarcoma that much more difficult. Research into sarcoma, like other rare diseases, is stymied by how rare these cancers are, but Demetri’s work at the Dana-Farber Center offers much to be hopeful about. 
Demetri, who has had his share of practice-changing clinical breakthroughs, mostly notably with treating<a href="http://www.gistsupport.org/"> gastrointestinal stromal tumors</a>, is excited by some of the preliminary research 23andMe is already compiling around our Sarcoma research community. He said the model for our research platform – crowd-sourced, Internet-based, and web-driven genetic studies – is something he has long envisioned as a way to improve medical research and treatment.
23andMe: You anticipated using the Internet to connect patients to doctors and researchers long before 23andMe created its Sarcoma Community. Where did that idea come from, and how does 23andMe’s work mesh with what you’d hope to see?
Demetri: For me, the idea of using the Internet was about finding the right patients with the disease under interest because it was very clear that the tools we use to diagnose a disease are not sufficiently powerful &#8230; cancer, it’s not one disease. Sarcomas under the microscope look very different. When we started diving into the chromosomes, they were completely different. And when we started diving into the genetics, they couldn’t be more different … When you peer into that looking glass, you see a thousand different kinds of sarcomas. You run into a problem if they are only one percent of all cancers and you have 1,000 different diseases; there are not a lot of people with any one kind of those cancers … You have to do the E-Harmony trick. You have to match the right patients to the right drugs. 23andMe is the perfect tool for that. 
Nine out of ten cancer drugs we have today fail in clinical trails and that’s because nobody’s paying attention to this important matching of what’s driving the patient with the cancer to the drug that works for that cancer. To do that you need to put another filter on the traditional clinical trials methodology where you don’t just take everybody who walks in the door with a given type of cancer. Instead, you take the patients with the right kind of genetics, and you actually select for them.It’s the same kind of issue that patients have. They want their medicine personalized. And you know, we hear a lot of backlash about this in the medical community where they are saying: 
“You guys in academia talk a lot about personalized medicine. Well, I’m very personalized. I treat my patients as individuals.” 
And you know they do. They do the best they can with old technology and old diagnostics, but the truth is our technology has moved beyond that, and patients want access to it.
23andMe: What might the work on Sarcomas mean for other kinds of research?
Demetri: Sarcomas tend to be driven by one dominant pathway, where if you shut it off, the cancer gets better. GIST (gastrointestinal stromal tumors) is a great example of that. But more common cancers are probably driven by two, or maybe three, mutated pathways or different dysregulated pathways – kind of like HIV. We didn’t see people living with HIV for years, and, years, and years until we got to triple therapy. So the challenge for us now in cancer is how to identify the right molecular pathways, do the clinical trials, and, as quickly as possible, move from using a single targeted drugs to giving triple therapies.
23andMe: More than 800 people are enrolled in our Sarcoma Community and are heading to 1,000. What is the significance of having that many people with Sarcoma in a research cohort?
<img loading="lazy" decoding="async" class="alignright size-medium wp-image-11554" title="George&amp;graph" src="https://blog-api.23andme.com/wp-content/uploads/2012/03/Georgegraph-300x200.jpg" alt="" width="300" height="200" srcset="https://blogcms.23andme.com/wp-content/uploads/2012/03/Georgegraph-300x200.jpg 300w, https://blogcms.23andme.com/wp-content/uploads/2012/03/Georgegraph-768x512.jpg 768w, https://blogcms.23andme.com/wp-content/uploads/2012/03/Georgegraph-1024x683.jpg 1024w, https://blogcms.23andme.com/wp-content/uploads/2012/03/Georgegraph-880x587.jpg 880w, https://blogcms.23andme.com/wp-content/uploads/2012/03/Georgegraph-1180x787.jpg 1180w" sizes="auto, (max-width: 300px) 100vw, 300px" />
Demetri: In research, in general, the quality of the community and its engagement are important. It’s not just the number. But it is incredibly helpful to be able to dialogue back and forth between patients, doctors, and researchers. Patients also want to be able to reach out to other patients. What I see in this tool is that possibility. 
Having patients participate as part of the research will teach us a lot. It’s to the patient&#8217;s advantage to help us hone the data we’re collecting and to have their voices heard. Simply knowing things like, ‘How did you feel taking this drug?’ That’s important. I think patients are frustrated that the health care system doesn’t already use that kind of data, their data, in an aggregated way.
23andMe: You are an excellent combination of someone who is both very realistic and optimistic. What would you tell someone today who was just diagnosed with Sarcoma?
Demetri: Sarcoma is a scary diagnosis, but some may proceed with a nihilism that’s unwarranted. That nihilism is the first thing we’ve tried to counteract in the last decade. I think the important thing with this is today, half of all patients will be cured with conventional modalities. That’s terrific. That’s number one, and even when we have somebody who doesn’t currently have the potential of being cured, I’ve been lucky enough to be part of developing drugs that made people who thought that they maybe had only had six weeks to live to still be alive 11 years later now. That is life-changing. That is a transformational kind of research. And I’ve seen the power of that kind of research. I tell my patients I’m going to help them make decisions so that they buy as much time as possible because we never know in research when we’re going to make the next major breakthrough that will make an incurable disease curable or a fatal one into one that will be manageable.

Talking about Sarcoma with George Demetri

<div style="float: right; text-align: justified; width: 200px; background-color: #eee; padding: 15px; margin-left: 10px;"><iframe loading="lazy" src="https://player.vimeo.com/video/34531632?title=0&amp;byline=0&amp;portrait=0&amp;color=1d2d85" width="200" height="115" frameborder="0"></iframe>Finding Your Roots Finding Your Roots With Henry Louis Gates, Jr. is a 10-part series in which the Harvard scholar will delve into the genealogy and genetics of famous Americans. Gates uses history and science, including 23andMe’s ancestry tools, to explore race, family and identify in each episode. With the help from expert genealogists, historians and scientists –two of 23andMe’s own helped in the work – Gates reveals fascinating stories and interesting surprises in the family histories of Kevin Bacon, Robert Downey, Jr., Brandford Marsalis, John Legend, Martha Stewart, Barbara Walters and many others. 
23andMe’s Senior Director of Research, Joanna Mountain, is a geneticist who worked as a consultant on the series and was interviewed for a few of the episodes. Mountain, who completed her Ph.D. in Genetics at Stanford University, is also a guest blogger for the series. Her post below first appeared on the Finding Your Roots program page. We’re republishing it here with the permission of PBS.</div>
By Joanna Mountain, Ph.D.,  Senior Director of Research 23andMe
As a geneticist at 23andMe, I combine my understanding of human prehistory and DNA variation to develop tools that help people answer one of the more fundamental questions we ask ourselves:
“Where am I from?”
It’s always fascinating and often surprising to answer that question, as the powerful stories in PBS’s series “Finding Your Roots” illustrate.
Intriguingly, the question “Where are you from?” has a precise meaning for many eastern Africans, as I learned when I was a Peace Corps volunteer in Kenya.
I always respond to that question with “California,” where I have lived most of my life, rather than “England” where I was born.
But unlike many Americans, Kenyans often respond to that question with a description of their ancestral origins – the place and its people. They may never have visited the place or people, but that is where they are “from.”
The answer to this question about our deeper ancestry allows us to connect with our ancestors of hundreds or thousands of years ago.
If we go back far enough in human history the answer to the question “where are you from” is the same for everyone:
“We’re from Africa.”
But telling someone that “we are all from Africa” doesn’t really answer the question about a person’s origins.
Our DNA has no sense of where we live or where we were born, but it does point directly to our deeper ancestry and to where our ancestors were living over the last few thousand years. This power of DNA to answer questions about human prehistory is what drew me to genetics in the first place. Solving puzzles and mysteries has always fascinated me.
My passion for genetics is also rooted in Africa, in Kenya specifically, where I taught math and science as a Peace Corps volunteer 25 years ago. The mystery I came across there was in the faces, languages and diets as well as other cultural practices of the people I met. I couldn’t help being fascinated by the diversity. The tall, slender Nilotic-speaking Maasai of southwestern Kenya differ in so many ways from the Bantu-speaking Mijikenda who live on the eastern coast where I was teaching. I left Kenya mystified by the origins of that diversity.
<img loading="lazy" decoding="async" class="alignright size-medium wp-image-11489" title="Joanna in Kenya" src="https://blog-api.23andme.com/wp-content/uploads/2012/02/Joanna-in-Kenya-300x199.jpg" alt="" width="300" height="199" srcset="https://blogcms.23andme.com/wp-content/uploads/2012/02/Joanna-in-Kenya-300x199.jpg 300w, https://blogcms.23andme.com/wp-content/uploads/2012/02/Joanna-in-Kenya-768x510.jpg 768w, https://blogcms.23andme.com/wp-content/uploads/2012/02/Joanna-in-Kenya-1024x680.jpg 1024w, https://blogcms.23andme.com/wp-content/uploads/2012/02/Joanna-in-Kenya-880x584.jpg 880w, https://blogcms.23andme.com/wp-content/uploads/2012/02/Joanna-in-Kenya-1180x784.jpg 1180w" sizes="auto, (max-width: 300px) 100vw, 300px" />
Shortly after I returned home to California, a friend introduced me to a famous geneticist at Stanford University, <a href="https://en.wikipedia.org/wiki/Luigi_Luca_Cavalli-Sforza#External_links">Luca Cavalli-Sforza</a>, who would give me the tools to solve that mystery. Cavalli-Sforza, who recently celebrated his 90th birthday, taught me the basics of DNA and the theories of population genetics. Together we poured over genetic data of peoples from all continents. Our goal was to discern the broad patterns of ancient human migrations.
I went on to earn my PhD in genetics, delving more deeply into the mysteries of human prehistory. Throughout my research I returned to focus on Africa, trying to understand the diversity that I had observed in Kenya. My research, conducted with collaborators from around the world, helped reveal the general shape of the history of African peoples over the last 100,000 years. We now believe that the ancestors of living peoples began to move from eastern or southern Africa into other parts of the continent by 75,000 years ago. This early spread within Africa explains the high level of genetic diversity in the continent today.
The diversity among the people of Kenya that I noticed over two decades ago, which sparked my interest in the study of genetics, has been explained in part by migrations into eastern Africa of people speaking all the major languages of Africa. We’ve learned this by combining genetic information with archaeological and linguistic evidence.
In the same way that we can understand the diversity within Africa, we can understand the diversity of all living people by studying DNA, archaeology and languages. Both the origins of humankind in Africa and the patterns of subsequent migration within and outside of Africa are written in the DNA of living people. We all share a common history in Africa, but the DNA of people both within Africa and elsewhere has differentiated over time as people migrated across the planet, becoming, until the last few hundred years, more and more isolated from one another.
Now that we know how DNA aligns with prehistoric migrations, we can trace the DNA of individuals to northern Europe or Central Asia, South America or the Near East, western Africa or Oceania. That information about where DNA is from can, in turn, answer questions about our ancestors. Were they struggling to feed their children through hunting red deer in northern Europe, harvesting shellfish in southeastern Asia, raising alpacas in the highland plateaus of western South America, or digging for tubers in eastern Africa? DNA shows that some of us have ancestors who faced the challenge of survival using several of these strategies.
<iframe loading="lazy" src="https://www.youtube.com/embed/xnZWMOpmoRk" width="420" height="315" frameborder="0"></iframe>
When Henry Louis Gates sits down with his guests and tells them their story of “where they are from” and explains their ancestry, it is a story that was written in their DNA many generations ago.
Joanna Mountain is a geneticist who is a consultant to the PBS series “Finding Your Roots,” and consulted previously on the PBS series “Faces of America.” Dr. Mountain completed her PhD in Genetics at Stanford University and has spent over 20 years studying human genetic diversity. Currently, she is Senior Director of Research at <a href="https://www.23andme.com/">23andMe, Inc.</a>

Senior Director of Research, 23andMe

Joanna Mountain

Solving Mysteries via DNA

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Today, February 29, is <a href="http://rarediseaseday.us/" target="_blank" rel="noopener noreferrer">Rare Disease Day</a>, a concept first initiated by the European Rare Disease Organization (EURORDIS) and now recognized worldwide.
When we think about diseases we often describe them as either common or rare. Common conditions – like heart disease and obesity – are complex in nature, meaning they are influenced by genetics and the environment. Conversely, most rare diseases are strongly influenced by genetics and less so by the environment. We hear a lot about common conditions because so many people have them, and in contrast, relatively little about rare diseases. But how rare is rare?
In the United States, a disease is defined as “rare” if it affects <a href="http://rarediseaseday.us/about/" target="_blank" rel="noopener noreferrer">fewer than 200,000 individuals</a> or roughly one in 1500. Rare diseases are often poorly understood, with symptoms that can be difficult to diagnose and can be life-threatening. Around 6,800 rare diseases have been identified and the large majority of them – up to 80% – are thought to have a genetic origin. Most rare diseases can’t be cured, and many lack effective treatments because research on rare conditions is often hampered by a scarcity of study participants and poor funding.
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<img loading="lazy" decoding="async" class="alignnone size-medium wp-image-11402" src="https://blog-api.23andme.com/wp-content/uploads/2012/02/Global-Genes-Project-300x278.png" alt="" width="300" height="278" srcset="https://blogcms.23andme.com/wp-content/uploads/2012/02/Global-Genes-Project-300x278.png 300w, https://blogcms.23andme.com/wp-content/uploads/2012/02/Global-Genes-Project-768x712.png 768w, https://blogcms.23andme.com/wp-content/uploads/2012/02/Global-Genes-Project-880x816.png 880w, https://blogcms.23andme.com/wp-content/uploads/2012/02/Global-Genes-Project.png 954w" sizes="auto, (max-width: 300px) 100vw, 300px" />
Join the Global Genes Projectâ„¢ and help unite one million people for rare diseases. The Global Genes Projectâ„¢ is a campaign that works to help individuals and organizations participate in this annual day of recognition for rare diseases. Getting involved can be as simple as putting on a pair of genes (ahem, jeans) – because 80% of rare diseases have a genetic origin – or as involved as organizing a local Denim &amp; Genes event.
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If you add up all the rare diseases, about 30 million Americans suffer from a rare disease. That’s nearly 10% of the population—suddenly, rare is not so rare! You’ve likely heard of at least some of these conditions, and 23andMe provides health reports for many of them, from cystic fibrosis to sickle cell anemia.
23andMe believes that our innovative research model can improve the treatment of rare diseases. So far, we’ve launched research initiatives for two rare diseases—myeloproliferative neoplasms (MPNs) and sarcoma—to better understand their causes and help bring about treatments. We are currently enrolling participants in both studies, so join our cause if you suffer from one of these disorders or know of someone who does.

News — Page 27