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

23andMe Blog

23andMe Blog Team

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

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

Research participants have a right to their own genetic data

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

Ewwww: Cruise Ship Cleanliness Not What It Should Be

<img loading="lazy" decoding="async" class="alignright size-full wp-image-5253" title="iStock_000003313784XSmall" src="https://blog-api.23andme.com/wp-content/uploads/2009/10/iStock_000003313784XSmall.jpg" alt="iStock_000003313784XSmall" width="313" height="233" srcset="https://blogcms.23andme.com/wp-content/uploads/2009/10/iStock_000003313784XSmall.jpg 401w, https://blogcms.23andme.com/wp-content/uploads/2009/10/iStock_000003313784XSmall-300x224.jpg 300w" sizes="auto, (max-width: 313px) 100vw, 313px" />
New research suggests that your skills behind the wheel may be affected by your genes.
To better understand the effects of a variant in the BDNF gene on motor skills learning, Steven Cramer and colleagues at UC Irvine tested 29 subjects in a driving simulator. Their results, published in the journal Cerebral Cortex, might make you think twice about whom you go on your next road trip with.
Subjects sat in front of a screen with their hands firmly planted at &#8220;10 and 2&#8221; on a steering wheel and guided their &#8220;car&#8221; around a track, attempting to stay centered over a black line. The steering was tuned so that subjects had to begin turning before the screen actually changed.
Over the course of 15 trials, all of the study subjects got better at the driving task. But the seven people with a specific variant improved less than the others. When subjects returned to the lab four days later for a final lap, everyone had forgotten how to drive the simulator a little bit, but they did even worse.
&#8220;These people [the variant] make more errors from the get-go, and they forget more of what they learned after time away,&#8221; Cramer said in a press release.

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

The Bad Driving Gene?

<img loading="lazy" decoding="async" class="alignright size-full wp-image-5233" title="iStock_000000481784XSmall" src="https://blog-api.23andme.com/wp-content/uploads/2009/10/iStock_000000481784XSmall.jpg" alt="iStock_000000481784XSmall" width="320" height="236" srcset="https://blogcms.23andme.com/wp-content/uploads/2009/10/iStock_000000481784XSmall.jpg 403w, https://blogcms.23andme.com/wp-content/uploads/2009/10/iStock_000000481784XSmall-300x222.jpg 300w" sizes="auto, (max-width: 320px) 100vw, 320px" />
<a href="http://www.medco.com/medco/corporate/home.jsp" target="_blank" rel="noopener noreferrer">Medco Health Solutions, Inc.</a>, announced this week that it will conduct a clinical trial to assess whether clopidogrel bisulfate (Plavix ®, Bristol-Myers Squibb and Sanofi-aventis) is just as effective as the newer drug prasugrel (Effientâ„¢, Eli Lilly and Company) in people who lack a genetic variation that inhibits their metabolism of clopidogrel. This new research has important implications for both patient safety and health care costs.
Both clopidogrel and prasugrel are anti-platelet medications that reduce the ability of blood to form clots. The drugs are used to reduce the risk of a heart attack and stroke in people who have suffered from a recent cardiovascular event, and in those who have peripheral artery disease, unstable angina or a stent.
Variations in the CYP2C19 gene that prevent clopidogrel from being converted into its active form in the body have been shown to prevent patients from receiving the drug&#8217;s full benefit. People with these gene variations who are taking clopidogrel may be at a higher risk for heart attacks, strokes and death from cardiovascular causes than those whose genetics allow them to metabolize the drug.
(Prasugrel is metabolized through a different biological pathway than clopidogrel, and is not affected by CYP2C19 variants.)
Medco&#8217;s study will assess patients&#8217; rates of nonfatal heart attacks, nonfatal strokes and cardiovascular deaths after six months of treatment with either clopidogrel or prasugrel. Researchers will be looking to see if there is any difference between those patients who are taking clopidogrel, and whose genetics predict that they should be able to metabolize it–and those patients who are taking prasugrel.
&#8220;Plavix is going generic in 2011 and if found to be equally effective as Effient for patients who have a normally functioning version of the CYP2C19 gene, the study provides the evidence that would allow these patients to opt for a lower cost treatment,&#8221; said Medco&#8217;s chief medical officer Dr. Robert Epstein in a press release.
Former U.S. Secretary of Health and Human Services Michael O. Leavitt was quoted in the Medco press release as saying, &#8220;Studies like this are necessary to show how innovation can derive greater value from what we spend on health care.   A simple test can identify a drug&#8217;s ability to work for a particular patient or point them to another one that could provide a better outcome. Personalized medicine is the new frontier in making medication safer and more effective. What we learn from this study, and others like it, will save lives and money.&#8221;
Patients aren’t the only ones who would save if Medco&#8217;s research shows that the soon-to-be generic clopidogrel is an effective choice for them. An Associated Press story notes that generic drugs are more profitable for Medco than higher-priced brand name products.
Comparative effectiveness research has received a lot of attention in the United States health care debate lately.   Some worry that it will result in policies that are not in patients&#8217; best interests.
&#8220;We need to be mindful of the goal of comparative effectiveness research and not lose all that we have gained in understanding how individuals differ and how that could be factored into better diagnostics and preventive strategies,&#8221; said National Institutes of Health (NIH) director Francis Collins, speaking at a recent American Association for the Advancement of Science <a href="https://www.reuters.com/article/healthNews/idUSTRE59P4UD20091026?feedType=RSS&amp;feedName=healthNews&amp;pageNumber=1&amp;virtualBrandChannel=0" target="_blank" rel="noopener noreferrer">forum on personalized medicine</a>.
Collins recommended that genetic factors be included in comparative effectiveness research (as is the case in Medco&#8217;s study), to make sure that treatments that work for specific groups of patients are not &#8220;lost in the wash by considering everybody equivalent.&#8221;
The Genotype-Guided Comparison of Clopidogrel and Prasugrel Outcomes Study (GeCCO) is part of Medco&#8217;s “<a href="http://www.genomeweb.com/dxpgx/medcos-new-idea-pgx-program-generics-dispense-smarter-treatments-and-increase-sa" target="_blank" rel="noopener noreferrer">Genetics for Generics</a>” program and is <a href="http://clinicaltrials.gov/ct2/show/NCT00995514?term=NCT00995514&amp;rank=1" target="_blank" rel="noopener noreferrer">registered with the NIH</a>.
Related Blog Posts: 
<a href="https://blog.23andme.com/articles/more-evidence-that-genetics-can-reduce-the-efficacy-of-anti-clotting-medication-clopidogrel" target="_blank" rel="noopener noreferrer">More Evidence that Genetics Can Reduce the Efficacy of Anti-Clotting Medication Clopidogrel</a> 
<a href="https://blog.23andme.com/2008/12/23/snpwatch-genetic-variants-may-reduce-ability-of-anti-clotting-drug-clopidogrel-to-prevent-a-second-heart-attack/" target="_blank" rel="noopener noreferrer">SNPwatch: Genetic Variants May Reduce Ability of Anti-Clotting Drug Clopidogrel to Prevent a Second Heart Attack</a>

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

<img loading="lazy" decoding="async" class="alignright size-full wp-image-5207" title="Hutterer-Frauen_bei_der_Arbeit" src="https://blog-api.23andme.com/wp-content/uploads/2009/10/Hutterer-Frauen_bei_der_Arbeit.jpg" alt="Hutterer-Frauen_bei_der_Arbeit" width="300" height="224" />
There are over 50,000 people in North America who define themselves as Hutterites, though you probably have never met one. One of the main branches of the <a id="yg7o" title="Anabaptists" href="https://en.wikipedia.org/wiki/Anabaptist" target="_blank" rel="noopener">Anabaptists</a>, Hutterites live in self-sustaining communities throughout the rural northwestern United States and Canada. 
Like their sister branches, the Amish and the Mennonites, the history and culture of the Hutterites have long fascinated scholars. But there have been few forays into the genetics of this unique community – until now. In the October 21 issue of the <a href="https://www.nature.com/ejhg/journal/vaop/ncurrent/abs/ejhg2009172a.html" target="_blank" rel="noopener">European Journal of Human Genetics</a>, geneticist Irene Pichler and an international team of experts set out to unravel the genetic history of the Hutterites.
The history of the Hutterites goes back over 500 years, to a stretch of land in northernmost Italy called Tyrol. It was here that a small group of people, led by local hatmaker Jakob Hutter, formed a religious community centered on absolute pacificism and communal living. The Hutterites, as they came to be known, were part of the <a href="https://en.wikipedia.org/wiki/Radical_Reformation" target="_blank" rel="noopener">Radical Reformation</a>, which rejected the teachings of both the Roman Catholic Church and the more moderate Protestant movement. 

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

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

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

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

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

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


Photo courtesy of Wikimedia Commons.

The Genetic Origin and History of the Anabaptist

<img loading="lazy" decoding="async" class="alignright size-full wp-image-5313" title="wolf" src="https://blog-api.23andme.com/wp-content/uploads/2009/10/wolf1.jpg" alt="wolf" width="350" height="260" srcset="https://blogcms.23andme.com/wp-content/uploads/2009/10/wolf1.jpg 350w, https://blogcms.23andme.com/wp-content/uploads/2009/10/wolf1-300x223.jpg 300w" sizes="auto, (max-width: 350px) 100vw, 350px" /> 
Lupus, which means &#8220;wolf&#8221; in Latin, gets its name from the skin manifestations sometimes seen in the disease. A physician in the 13th century thought they looked like wolf bites.
In autoimmune disorders, the immune system – which normally protects us from harmful, foreign substances – goes into overdrive and starts attacking the body&#8217;s own cells, causing inflammation and organ damage.
<a href="http://www.nlm.nih.gov/medlineplus/ency/article/000435.htm">Systemic lupus erythematosus</a> (SLE) is an autoimmune disease characterized by chronic, widespread  inflammation that can result in arthritis, fever, skin rashes, muscle aches, seizures and fatigue, among other symptoms.  Some symptoms can even be life-threatening. Between one and seven out of every 10,000 people is affected by SLE. The disease affects women nine times more frequently than men, and tends to be more prevalent and severe in people of non-European descent.  The exact causes of SLE are unknown and there is currently no cure.
For several decades now, researchers have probed the genetic underpinnings of this mysterious disease. Two studies published this week in Nature Genetics identify new genetic variants associated with SLE in European and Asian populations.
In the <a href="https://www.nature.com/ng/journal/vaop/ncurrent/abs/ng.468.html">first study</a>, a team led by Vesela Gateva and Robert Graham of Genentech identified ten novel genetic variants associated with SLE in a European group consisting of more than 3,000 people with the disease and 10,000 people without SLE. Half of these variants were previously associated with other autoimmune diseases, but this is the first time they have been associated with SLE. In addition, the researchers confirmed nine variants previously linked to SLE in other studies.
Of the previously reported autoimmune variants, Gateva and colleagues note that the A version of the variant is also a known risk variant for age-related macular degeneration, seems to be protective against SLE, although additional research will be needed to confirm this effect.
One of the SNPs not previously associated with SLE or any other autoimmune disease,   is in the gene that encodes TNIP1.   The TNIP1 protein is known to interact with TNFAIP3, a protein that genetic studies have previously linked to rheumatoid arthritis, psoriasis and type 1 diabetes – all autoimmune disorders – suggesting that the TNIP1-TNFAIP3 association may play a general role in autoimmunity.
In the <a href="https://www.nature.com/ng/journal/vaop/ncurrent/abs/ng.472.html">second study</a>, Jian-Wen Han and Xue-Jun Zhang’s team from Anhui Medical University in China identified 21 genetic variants associated with SLE in more than 4,000 Chinese individuals with the disease and 8,200 individuals without autoimmune disorders. About half of the associations confirmed previous reports in European populations, and half represented novel findings.
Interestingly, one of the new variants they identified is also in the TNIP1 gene. Here, each copy of a T increased odds of SLE by about 1.24 times. Many other SNPs associated with SLE in the Chinese study were located in or near genes involved in immune response.
The TNIP1-TNFAIP3 connection and association of variants known to be linked to other autoimmune diseases add to growing evidence that common genetic factors contribute to autoimmunity. These findings may help pave the way for novel therapeutics for autoimmune disease that exploit this shared genetic basis.

New Variants Associated With Lupus in Europeans and Asians

<img loading="lazy" decoding="async" class="alignright size-full wp-image-5106" title="iStock_000006370742XSmall" src="https://blog-api.23andme.com/wp-content/uploads/2009/10/iStock_000006370742XSmall.jpg" alt="iStock_000006370742XSmall" width="350" height="263" srcset="https://blogcms.23andme.com/wp-content/uploads/2009/10/iStock_000006370742XSmall.jpg 400w, https://blogcms.23andme.com/wp-content/uploads/2009/10/iStock_000006370742XSmall-300x225.jpg 300w" sizes="auto, (max-width: 350px) 100vw, 350px" />
Previously we discussed two papers that identified <a href="https://blog.23andme.com/articles/snpwatch-genetic-variations-influencing-hemoglobin-levels-identified/">genetic variants associated with hemoglobin levels</a> in circulating blood.
But blood consists of much more than hemoglobin. It is responsible for much more than just transporting oxygen. This week Nature Genetics published the results of two of the largest blood studies to date. Together the studies identified dozens of new variants associated with nine blood-related traits.
<h6>Cellular Components</h6>
In addition to red blood cells, which carry hemoglobin, whole blood contains white blood cells. White blood cells are a crucial part of our immune system. Whole blood also contains platelets, which are important for clotting. All of these cellular components are suspended in a protein-rich plasma that makes up most of the volume of blood, and maintains the pressure needed to deliver the blood&#8217;s cargo throughout a person’s body.
Like hemoglobin levels, measurements of other blood traits can be informative about health. An abnormally high white blood cell count and platelet volume have both been linked to an increased risk for heart attack. These measurements can also indicate the presence of infectious disease, immunological disorders or cancers.
<a href="https://dx.doi.org/10.1038/ng.467">Nicole Soranzo and her colleagues in the HaemGen consortium</a> measured hemoglobin concentration (Hb), red blood cell count (RBC), red blood cell volume (MCV), platelet count (PLT), platelet volume (MPV), white blood cell count (WBC), the amount of hemoglobin per red blood cell (mean corpuscular hemoglobin content, or MCH), and the amount of hemoglobin relative to the size of the cell (mean corpuscular hemoglobin concentration, or MCHC) in more than 14,000 healthy individuals from Europe. They found sixteen new genetic associations with blood traits from fifteen genomic regions not previously thought to be involved.
<a href="https://dx.doi.org/10.1038/ng.466">Santhi Ganesh and her colleagues in the CHARGE consortium</a> measured Hb, MCV, RBC, MCH, MCHC, and the percent of red blood cells in whole blood (hematocrit, or Hct) in more than 24,000 Caucasian individuals from the U.S. and Europe. Here, they found nine new associated variants from eleven previously unassociated genomic regions.
One of the advantages of these studies is the number of traits that they analyzed.
“Until now, few genome-wide association studies have looked beyond single traits,” said co-author Christian Geiger. “But, through a systematic analysis of correlated traits we can begin to discover such shared genetic variants, forming the basis for understanding how these processes interact to influence health and disease.”
<h6>Coronary Artery Disease</h6>
Both teams noted several genomic regions that play a broad role in blood-related health. The HBS1L-MYB, TFR2-EPO, TMPRSS6 and HFE regions were all associated with at least three different traits. These regions have also been connected to fetal hemoglobin levels. They&#8217;re also connected to the iron-overload condition hemochromatosis. Of these newly associated variants, many are close to genes that present promising candidates for further research.
Soranzo’s team went further by investigating whether two of the variants associated with increased platelet volume (PLT) were also associated with coronary artery disease. They analyzed these SNPs in about 9,500 people with coronary artery disease and 10,500 healthy controls. They found that both variants increased odds of coronary artery disease by about 1.15 times.
<h6>Protection from Infection</h6>
When the researchers looked more closely at the region where and are located, they found a block of ten SNPs that tend to be inherited together. They are all associated with increased PLT and risk of coronary artery disease. They also confirmed previous findings from other researchers of association between celiac disease and type 1 diabetes with SNPs in this block.
Data for chimpanzees and multiple human populations point to a relatively recent event in human evolution. This was where the above-mentioned genetic variants swept across European populations. However this was not the case in East Asian or African populations.
The block of SNPs is located in an area of the genome involved in immune response. The authors suggest that these mutations may have given some populations a survival advantage against infection, despite increasing the risk for certain diseases.

Two Large Studies Identify More Variants Associated with Blood-Related Traits

<img loading="lazy" decoding="async" class="alignright size-full wp-image-5157" title="migraine" src="https://blog-api.23andme.com/wp-content/uploads/2009/10/migraine.jpg" alt="migraine" width="354" height="252" srcset="https://blogcms.23andme.com/wp-content/uploads/2009/10/migraine.jpg 435w, https://blogcms.23andme.com/wp-content/uploads/2009/10/migraine-300x214.jpg 300w" sizes="auto, (max-width: 354px) 100vw, 354px" />
Here’s how it goes for me: a few afternoons a year, usually when I haven’t slept or eaten right, but sometimes for no apparent reason, I begin to sense a pressure behind my left eyebrow and to feel queasy.
<h6>Migraines</h6>
By now I know what’s coming, and I resign myself to another miserable evening and a coming day or two lost to indistinctness. I rush home and secrete myself in the coolest, darkest spot I can find, because for each of my senses the volume seems to have been cranked to amphitheater-level. I lie there for four or five hours, a dog on a leash, thinking grim thoughts and, despite myself, yelping every now and again when the pain ratchets up.
Perhaps you know somebody with migraine and are familiar with the vocabulary they use to capture the experience: &#8216;throbbing&#8217;, &#8216;nauseating&#8217;, &#8216;excruciating&#8217; and the like. All true.  Respite comes only when my stomach has had too much and returns my lunch –  normally one wants to avoid this outcome, but here I welcome it, court it even, which I&#8217;ve always found darkly funny. Then I fall into a dreamless sleep. While some don’t have it as bad as me, many have it far worse.
<h6>New Migraine Headache Survey</h6>
With the launch of our new migraine headache survey today, we at 23andMe invite you all to share your headache experiences, whether you&#8217;re one of the lucky few who&#8217;s never had even a little one or someone who must deal with the threat of migraine pain on a daily basis.  
You needn&#8217;t be a 23andMe customer to take the survey (although we recommend it). All you need is a <a title="Link to Free 23andMe Account Signup" href="https://www.23andme.com/user/signup/" target="_blank" rel="noopener">free 23andMe account</a>.

Migraine headaches are nasty things.
The common feature is a terrible pulsing pain emanating from inside the skull, usually just on one side, but apart from this everyone experiences them a bit differently. Some unlucky folks get them every day, while others get them just once a year. Migraines can last for a few hours or can pound on for days at a time. Then there is the menagerie of symptoms that can accompany the headaches, including nausea, vomiting, visual or aural illusions, and aversion to light, smell, touch and/or sound.
Perhaps most variable across people are the causes of the headache, or triggers. For one person the triggers might be red wine or nuts, for another they might be stress, bright lights, or noise.
There is a wide array of treatment options for migraine. With guidance from their doctors, most migraine sufferers nowadays are able to find partial or full relief from their headaches. Despite the effectiveness of these treatments, the basic biology of the disease is not well-understood1,  and migraine continues to exact a tremendous physical and economic toll on our society2.
<h6>More Research Needed</h6>
Two prominent migraine researchers <a title="Shapiro RE &amp; Goadsby PJ, Cephalalgia (2007)" href="https://www.ncbi.nlm.nih.gov/pubmed/17727471" target="_blank" rel="noopener">have suggested</a> that the blame for the slow progress in understanding migraine lies with a systemic lack of public funding for migraine research. They argue that the relatively recent, and incomplete, acceptance of migraine by the medical and research communities as a genuine medical problem, as opposed to mere melodrama, has led migraine&#8217;s funding to lag well behind that for diseases of similar impact. For example, they estimate that while $13.80 is spent for each sufferer of asthma, just  36 cents of federal research funds are spent per migraine sufferer.
The genetics of migraine are also only partially understood.
That&#8217;s where our new survey comes in. Our community-based research program  <a title="Link to 23andWe Summary Page" href="https://www.23andme.com/research/" target="_blank" rel="noopener">23andWe</a> seeks to empower the public to engage in genetic research from the ground up. We know our efforts cannot substitute for proper federal support of migraine research, but evidence of great public interest, plus a new finding or two, would add to our understanding of the disease and potentially send a message to Washington.
With all haste, then, please head over to the new migraine survey and be counted!
 
Footnotes:
<ol>
<li>What is understood of its biology and chemistry is fascinating, and summarized well  <a title="&quot;Why Migraines Strike&quot;, by Dodick &amp; Gargus, Scientific American 2008" href="http://www.scientificamerican.com/article.cfm?id=why-migraines-strike" target="_blank" rel="noopener">here</a>.</li>
<li>Nearly 40 million people in the US, and a similar number in Europe, suffer from migraine, roughly one in every ten people. Migraine occurs in women about three times more commonly than in men. Migraine is estimated to cost  around <a href="https://www.ncbi.nlm.nih.gov/pubmed/18070057" target="_blank" rel="noopener">$23BN/year in the US </a>and <a href="https://www.ncbi.nlm.nih.gov/pubmed/17727472" target="_blank" rel="noopener">Euro27BN/year in Europe</a> in direct medical costs and in <a href="https://www.ncbi.nlm.nih.gov/pubmed/17426520" target="_blank" rel="noopener">indirect costs</a>, such as lost productivity.</li>
</ol>
 


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