<img loading="lazy" decoding="async" class="alignright size-full wp-image-5500" title="Lab mouse" src="https://blog-api.23andme.com/wp-content/uploads/2009/12/iStock_000003710874XSmall.jpg" alt="Lab mouse" width="357" height="251" srcset="https://blogcms.23andme.com/wp-content/uploads/2009/12/iStock_000003710874XSmall.jpg 413w, https://blogcms.23andme.com/wp-content/uploads/2009/12/iStock_000003710874XSmall-300x211.jpg 300w" sizes="auto, (max-width: 357px) 100vw, 357px" />
Even if you do everything right — exercise, healthy eating, no smoking&#8211; whether or not you&#8217;ll make it to the century mark depends to some extent on your genes.
<h6>FOXO3A</h6>
One of the important longevity genes seems to be FOXO3A.   It&#8217;s been linked to lifespan in several experimental animal models. In humans, studies have shown that certain variations in the FOXO3A gene increase the odds of being extremely long-lived.
It&#8217;s not exactly clear how FOXO3A affects longevity because it&#8217;s known to play a part in several important cellular functions, including cell growth, cell specialization, response to oxidative stress and   the regulation of cell death.   Two studies published last month in the journal Cell Stem Cell added to the list of the FOXO3A&#8217;s talents.
<h6>Brain Function and Repair</h6>
<a href="https://www.ncbi.nlm.nih.gov/pubmed/19896443" target="_blank" rel="noopener noreferrer">Renault et al.</a> and <a href="https://www.ncbi.nlm.nih.gov/pubmed/19896444" target="_blank" rel="noopener noreferrer">Paik et al.</a> showed that in mice FOXO3A and related FOXO genes are involved in maintaining the brain&#8217;s ability to generate new cells, a function critical for both normal brain functions and repair in response to natural degeneration or injury.
New brain cells arise from a pool of specialized self-renewing cells called neural stem cells.   The FOXO genes appear prevent the brain from burning through its supply of these important cells prematurely.
&#8220;Because [neural stem cells] have been shown to be important for learning, memory, and mood regulation, our findings could give insight into the decline in cognitive function that occurs during aging,&#8221; Renault et al. wrote in their report.
More research will be needed to fully understand the role of the FOXO genes in neural stem cells.   Experiments will also be needed to test whether these findings can be extended to humans.
Despite the work that is left to be done, Paik et al. optimistically suggest the new understanding of the importance of the FOXO genes in neural stem cells may help guide the development of drugs that could help improve central nervous system health in the elderly and people suffering from neurodegenerative disease or brain injury.

23andMe Blog

23andMe Blog Team

Mouse Studies Show that Longevity Gene May Play a Role In Maintaining Stem Cells in the Brain

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Looking for something to talk about between mouthfuls of green bean casserole and cranberry dressing?
Instead of discussing the big game or Friday&#8217;s shopping prospects, U.S. Surgeon General Regina Benjamin would like you to consider chatting up your relatives to learn their medical histories in honor of Family Health History Day.
“An important first step in preventing illness is learning about health conditions in our families that may put us at risk for inheriting diseases such as diabetes, heart disease, cancer, Alzheimer’s, mental illness, and many others,” said Dr. Benjamin in a press release.   “Discussing family health information with each other can often uncover things you never knew, simply because no one ever asked.”
Here are a few resources to help you get you started:
<h6>The U.S. Surgeon General’s Family History Initiative</h6>
You can use the online tool “My Family Health Portrait” to help guide you in collecting your own family’s health history. (Also available in Chinese, Polish, Spanish, French and Portuguese from the Brigham and Women’s Hospital National Family Health Initiative Website.)
<h6>The Genetic Alliance</h6>
Links to sites that can help with collecting a family health history, including resources for family reunion organizers who want to incorporate this into their next gathering.

Remember: Turkey Day is Also National Family Health History Day

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Type 2 diabetes is a common disease characterized by high blood glucose levels and unresponsiveness to insulin. Individuals with type 2 diabetes may produce insulin at normal levels but do not respond to it sufficiently, either because the insulin receptors in their cells have become less sensitive or because the insulin produced in the pancreas isn’t being delivered to other cells. One reason that insulin might not make it where it’s supposed to go is that insulin secretion from pancreatic Î²  cells is impaired.
In an article published in <a href="https://dx.doi.org/10.1126/science.1176827">Science</a> last week, Anders Rosengren, Erik Renstrom and their team from the <a href="http://www.ludc.med.lu.se/">Lund University Diabetes Centre</a> in Sweden used newly created rat strains — called N1I5 and N1I11, both derived from a well-studied type 2 diabetes strain — to identify the Adra2a gene as one of the genetic culprits behind defective insulin secretion. They then tied a variation in this gene to type 2 diabetes in humans.
When Rosengren and his colleagues stimulated Î²  cells from each strain with glucose, they found that N1I5 cells secreted less insulin than both N1I11 and normal cells. Other experiments verified that whatever was causing impaired insulin secretion was unique to N1I5.
Of the handful of possible gene candidates, only Adra2a showed different expression between the two strains, causing N1I5 cells to produce almost twice as much of the encoded Î±(2A)AR   protein as N1I11 cells. Additional experiments confirmed that Î±(2A)AR was indeed responsible for impaired insulin secretion. Î±(2A)AR is known to be involved in suppressing insulin secretion but variations in the gene had not previously been associated with the development of type 2 diabetes.
Based on the strong evidence from their rat experiments, Rosengren’s group hypothesized that variations in the human version of Adra2a, helpfully called ADRA2A, would contribute to type 2 diabetes risk in humans. Using two independent populations totaling about 5500 people, they first found that the less common A version of was associated with impaired insulin secretion.
To see whether the results extended to actual diabetes risk, Rosengren and his team then compared a group of 2830 type 2 diabetics to 3740 non-diabetics. They found that was also significantly associated with type 2 diabetes, with each copy of the A version increasing the odds of having the disease by about 1.4 times. The final piece of evidence came from laboratory experiments. Pancreatic cells from people carrying the riskier A version of behaved just like the cells from the insulin-secretion impaired N1I5 rats.

New Study Rats Out A Genetic Variant Associated with Type 2 Diabetes

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More than 30 million people worldwide are living with HIV, and about three million more are infected each year. Although people infected with the virus are living longer and healthier lives thanks to intense research, there is still no cure.
<h6>Fighting HIV and AIDS</h6>
One way to identify new strategies for fighting HIV is to look to those people whose bodies are naturally able to keep the virus as bay, at least for a time.
In <a href="https://www.ncbi.nlm.nih.gov/pubmed/17641165?ordinalpos=1&amp;itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_MultiItemSupl.PMC_FreeArticle_ad&amp;linkpos=1&amp;log$=pmcad6_article" target="_blank" rel="noopener">2007</a> researchers identified a variation near the HLA-C gene that was shown to affect the amount of virus present in the body after acute infection but before onset of AIDS symptoms.   This so-called &#8220;viral set point&#8221; correlates with rate of disease progression, infectiousness and response to treatment.
Now another set of researchers has yet again shown that this variant affects viral set point.
Their results, published online this week in the journal <a href="https://dx.doi.org/10.1038/ng.486" target="_blank" rel="noopener">Nature Genetics</a>, further show that this variant influences the time it takes to progress to AIDS.
<h6>Viral Loads</h6>
Rasmi Thomas and colleagues analyzed the DNA from 828 people infected with HIV, all of European ancestry.   Patients were divided into groups with low, medium and high viral loads (&lt;2,000 copies of viral RNA per milliliter of blood, 2,000-10,000 copies, and &gt;10,000 copies). About 62% of people with two Cs at had a viral load below 2,000, while only about 15% of people with two Ts controlled the HIV virus to this extent.   About 33% of people with CT at fell into the &#8220;controller&#8221; group.   These results agree with what was found by previous researchers.
In a separate group of 763 people infected with HIV (also all of European descent), the researchers found that the C version of was somewhat protective against progression from HIV infection to extremely low CD4 cell count, a measure of immune system strength.   The C version of this SNP also conferred some protection against progression to an AIDS-defining complications and death.
As noted above, low viral set point is known to correlate with slower progression to AIDS, but the analysis by Thomas et al. indicates that the effects of on viral set point and progression are at least somewhat independent.
The researchers examined blood from 50 health donors to investigate the function of .     They found that the C version was associated with increased HLA-C protein on the surface of immune cells.   They conclude that this increased protein expression must be what helps the body fight off HIV, although the details of how increased HLA-C is beneficial are still unknown.   Further research will be needed in order to translate these findings into new strategies for treatment or prevention of HIV infection.
<ul>
<li>When was initially identified as a variant that could affect HIV viral set point, researchers <a href="http://www.dukehealth.org/HealthLibrary/News/10080" target="_blank" rel="noopener">suggested that vaccines</a> designed to elicit an immune response mediated by HLA-C might be a good idea.   Perhaps this new research, which further solidifies the importance of HLA-C variation in virus control, will rekindle that idea, especially in light of recent HIV vaccine disappointments (more <a href="http://latimesblogs.latimes.com/booster_shots/2009/10/aids-vaccine-results-questioned.html" target="_blank" rel="noopener">here</a> and <a href="http://latimesblogs.latimes.com/booster_shots/2009/11/cold-virus-may-have-caused-2007-aids-vaccine-trial-failure.html" target="_blank" rel="noopener">here</a>).</li>
</ul>

Genetic Variant Affects HIV Viral Set Point and Disease Progression

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Inflammatory bowel disease (IBD) is a chronic autoimmune disorder encompassing Crohn’s disease and ulcerative colitis that affects more than a million people in the United States.
Our immune system usually works to fight off harmful pathogens that might pass through our digestive tract. In IBD, however, the immune system stays in overdrive and attacks normal intestinal cells. Chronic inflammation causes abdominal cramps, diarrhea, pain and fever, and weight loss.
<h2>New Research</h2>
Most studies of IBD have investigated genetic factors for Crohn’s disease, but a set of articles published this week in Nature Genetics on IBD address two less-explored angles.
Two studies identify new genetic associations with ulcerative colitis in European and Asian populations. The third study focuses on early-onset IBD (diagnosed before age 19), which is typically more severe than adult-onset IBD and is believed to have a more robust genetic component.
In a joint effort, the UK IBD Genetics Consortium and the <a href="https://www.wtccc.org.uk/ccc2/">Wellcome Trust Case Control Consortium 2</a> identified <a href="https://dx.doi.org/10.1038/ng.483">three genetic variants associated with ulcerative colitis</a> in 4,682 people with the condition and over 10,000 healthy individuals, all of European ancestry. These variants are located in regions of the genome that had not previously been associated with ulcerative colitis.
<h2>Intestinal Lining and Cell Interaction</h2>
Each of the three SNPs was associated with slightly increased odds of ulcerative colitis. The researchers highlight several proteins encoded by genes near these variants that help maintain the lining of the intestine and regulate cell-cell interactions, including HNF4a, E-cadherin, and laminin. However, their exact roles in ulcerative colitis are unclear.
The <a href="https://dx.doi.org/10.1038/ng.482">second study</a>, led by Kouichi Asano and Michiaki Kubo of the RIKEN Center for Genomic Medicine in Japan, looked for genetic variants associated with ulcerative colitis in a group of about 1,380 Japanese individuals with the disease and 3,050 individuals without it. Their two strongest associations were SNPs near genes involved in the immune response.
<h2>More on Immune Response</h2>
One of these SNPs is in a genome region that encodes antigen-presenting proteins, which are important for the immune system&#8217;s recognition of “self” vs. foreign substances. Antigen-presenting proteins display bits and pieces of proteins or sugars (antigens) from cells and other microorganisms to immune cells that generally ignore “self” antigens but destroy foreign ones. In autoimmune diseases like IBD, the immune system loses the ability to distinguish between the two types of antigens and mistakenly reacts to the body’s own cells.
The other strongly associated SNP is located in the FCGR2A gene and causes a change to the encoded protein, which is expressed on the surface of several types of immune cells. Previous studies by other groups have shown that this SNP can play a significant role in the development of other autoimmune disorders. The version of the SNP that increased risk for those other disorders is the opposite version compared to the version associated with increased risk for ulcerative colitis in the current Japanese study.
<h2>Early Onset</h2>
In the <a href="https://dx.doi.org/10.1038/ng.489">third study</a>, a team led by Marcin Imielinski and Hakon Hakonarson of the Children’s Hospital in Philadelphia identified genetic variants associated with early-onset IBD. Almost 3,500 individuals of European ancestry who had been diagnosed with IBD — either Crohn’s disease or ulcerative colitis — before their nineteenth birthday were compared to close to 12,000 individuals free of IBD.
Imielinski’s team identified three SNPs significantly associated with early-onset Crohn’s disease. For two of the SNPs, and , the less common version was associated with slightly increased odds of early-onset Crohn’s disease, while the less common version of was associated with slightly decreased odds. They also observed an association between and early-onset ulcerative colitis.
When they conducted a combined analysis of all early-onset IBD cases (Crohn&#8217;s and ulcerative colitis), the researchers found that the three genetic variants associated with early-onset Crohn’s disease were also associated with early-onset IBD in general. The effect sizes were similar to those seen when they looked at just Crohn&#8217;s disease. In addition, they identified another SNP associated with early-onset IBD.
<h2>Early Onset and Immune Response</h2>
Of the four genetic variants associated generally with early-onset IBD, Imielinski and his colleagues consider it to be especially important given its proximity to IL27, a gene involved in the immune system. The researchers showed in a small sample that individuals with early-onset Crohn’s disease express the gene at much lower levels than healthy people. IL27 encodes a protein that suppresses inflammatory immune cells in the intestine, so lower expression of IL27 may contribute to a hyperactive inflammatory response.
Although the biology of IBD is complex, these three studies contribute to a more comprehensive picture of the genetic factors underlying the condition and suggest potential directions for the development of therapeutics.
&#8220;This is an evolving story of discovering what genes tell us about the disease,&#8221; said Dr. Baldassano from the Children’s Hospital team in a <a href="http://www.eurekalert.org/pub_releases/2009-11/chop-lgs111209.php">press release</a>. &#8220;Pinpointing how specific genes act on biological pathways provides a basis for ultimately personalizing medicine to an individual&#8217;s genetic profile.&#8221;

Piecing Together The Inflammatory Bowel Disease Puzzle

Editor&#8217;s note: This no longer reflects 23andMe&#8217;s current product offering. We now offer <a href="https://www.23andme.com/dna-ancestry">DNA Relatives</a> as a way to connect with other customers with whom you share DNA.
Get ready &#8212; there&#8217;s a whole new way to do genealogy.
You may have already heard about a new feature 23andMe is offering its customers, called Relative Finder.
With the launch of our new Ancestry Edition, we wanted to tell you more about it.

<img loading="lazy" decoding="async" class="alignright size-full wp-image-5411" title="Picture 210" src="https://blog-api.23andme.com/wp-content/uploads/2009/11/Picture-210.png" alt="Picture 210" width="326" height="244" srcset="https://blogcms.23andme.com/wp-content/uploads/2009/11/Picture-210.png 326w, https://blogcms.23andme.com/wp-content/uploads/2009/11/Picture-210-300x225.png 300w" sizes="auto, (max-width: 326px) 100vw, 326px" />Don&#8217;t just settle for two branches of your family tree.
Relative Finder is a breakthrough feature that uses autosomal DNA to help you find relatives from all parts of your family tree. With Relative Finder, you can grow your family tree like never before, and discover relatives you never knew you had.
Relative Finder is available to people who buy the Ancestry or Complete Edition of the 23andMe service.

<h6>
How is Relative Finder Different? 
</h6>

Until now, DNA genealogy tests could only tell you about a small part of your family tree, because they only used DNA from the Y chromosome and mitochondria. By using autosomal DNA, Relative Finder can trace any ancestor, no matter where they are in your family tree.
What&#8217;s so special about autosomal DNA? The autosomal chromosomes, which make up most of our DNA, have the unique property of randomly mixing in specific ways when passed down from parent to child. The result is that we are a mosaic of DNA segments that we inherited from our ancestors.

<img loading="lazy" decoding="async" class="alignright size-full wp-image-5410" title="Picture 211" src="https://blog-api.23andme.com/wp-content/uploads/2009/11/Picture-211.png" alt="Picture 211" width="326" height="245" srcset="https://blogcms.23andme.com/wp-content/uploads/2009/11/Picture-211.png 326w, https://blogcms.23andme.com/wp-content/uploads/2009/11/Picture-211-300x225.png 300w" sizes="auto, (max-width: 326px) 100vw, 326px" />With Relative Finder, find relatives from all branches of your family tree!
To give an example of the benefits of using autosomal DNA for learning about your ancestors, let&#8217;s consider your four grandparents. When looking at the Y chromosome (if you are male), you can trace your lineage through your paternal grandfather. When looking at the mitochondria, you can trace your lineage through your maternal grandmother.
But this is only half of your grandparents! By using autosomal DNA, you can trace the lineages through all four grandparents. Extending this back 10 generations, instead of two ancestors detectable via Y and mitochondria, autosomal DNA can give you access to over 1000 ancestors and their descendants.

<h6>
Relative Finder in Action 
</h6>

Relative Finder takes advantage of autosomal DNA by looking for shared segments with other 23andMe customers, which indicate a common ancestor. We list your closest matches first, but also let you sort and filter on other criteria you find important. Interested in relatives living abroad, or a particular Y or mitochondrial haplogroup? We can help you find them.
Take your time &#8212; users with European ancestry often have more than 100 matches, and users with Ashkenazi Jewish ancestry often have more than 1000! As the 23andMe database grows, you&#8217;re likely to get even more matches.
Once you&#8217;ve found an interesting match, you can take the next step and contact them directly. Go ahead: Introduce yourself to that fifth cousin who lives in Macedonia, or your ninth cousin who lives just down the street. With Relative Finder, you can discover more about your ancestry than you ever thought possible!

<h6>
We Want You. 
</h6>

Up to now, we&#8217;ve been testing and tweaking Relative Finder extensively, both internally and with feedback from genealogy enthusiasts. Starting today, we are opening up that testing to all 23andMe customers who want the opportunity to experience Relative Finder.
During the remainder of this beta period, participants can instantly contact any potential relatives also participating in the beta.
By participating in the Relative Finder Public Beta, you will get early access to this revolutionary new feature. In return, we hope that you will send us feedback, suggest improvements and &#8212; most importantly &#8212; share your success stories.


We hope you enjoy taking your family tree to a whole new level with Relative Finder. After all, you never know who you might find.

Introducing Relative Finder: The Newest Feature from 23andMe

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 & 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.

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