New research by scientists at Vanderbilt University adds to our understanding of the legacy of our ancient cousins, the Neanderthals.<img loading="lazy" decoding="async" class="alignright wp-image-23459 size-medium" src="https://blog-api.23andme.com/wp-content/uploads/2016/01/Neanderthal-Image-247x300.jpg" alt="Neanderthal Image" width="247" height="300" />
<a href="http://science.sciencemag.org/content/351/6274/737.full">The study</a> looked specifically at health conditions, finding associations between Neanderthal DNA and conditions related to immune response, blood clotting, and depression by using electronic health records from more than 50,000 individuals.
When humans migrated out of Africa they intermixed with Neanderthals perhaps 60,000 years ago, and so all non-Africans carry some remnant of Neanderthal DNA. Scientists believe that by mixing with Neanderthals, who lived and thrived in Europe and Asia for 100,000 years, modern humans got an evolutionary advantage as they migrated into those new environments.
<a href="http://www.cell.com/ajhg/abstract/S0002-9297%2815%2900486-3">A paper</a> published earlier this year suggests that intermixing with Neanderthals conferred an advantageous immune response for populations that ultimately settled in Europe. Another study two years ago looked at how intermixing with another ancient human cousin, the Denisovan, may have conferred an evolutionary advantage for Tibetans to cope with high altitude through a variant in the EPAS1 gene that helps to prevent blood thickening.
But some of those same traits inherited from Neanderthals – and presumably other ancient human cousins – that tens of thousands of years ago may have been advantageous, may not be beneficial in modern times when diet and lifestyle are so different.
“These variants sometimes protect against a disease,” said Svante Paabo the<a href="http://www.mpg.de/9819763/neanderthal-genes-immune-system"> Max Planck Institute for Evolutionary Anthropology</a>.
Interviewed for a story in Science Magazine about the findings Paabo added that some of the variants may “sometimes make people more susceptible to disease.”
Although the Vanderbilt study focuses just on health related traits, it illustrates the potential of looking at a broad grouping of phenotypes like those in the electronic medical records, with known Neanderthal variants. (23andMe <a href="https://blog.23andme.com/articles/new-neanderthal-report">reports</a> to customers the number of Neanderthal variants they carry, how that compares with other customers, and traits those variants are associated with such as back hair and height.)
In an article in the<a href="http://www.theatlantic.com/science/archive/2016/02/neanderthal-dna-affects-depression-risk-today/462345/"> Atlantic</a>, Ed Yong points this out and notes that, instead of focusing on the associations with disease, attention around this study might be better focused on what those associations can tell us about the biology of certain conditions. For instance, the researchers found that Neanderthal DNA is associated with depression and certain mood disorders. Specifically, researchers speculate variants that helped Neanderthals adapt to lower sunlight exposure in northern latitudes, could have carried a higher risk for depression, which is influenced by sunlight exposure.

23andMe Blog

23andMe Blog Team

The Lasting Legacy of Neanderthals

Perhaps the stories are so interesting because they seem so improbable – tales of ordinary people faced with devastating genetic diseases<img loading="lazy" decoding="async" class="alignright size-thumbnail wp-image-23374" src="https://blog-api.23andme.com/wp-content/uploads/2015/12/Research-Icon-200x200.jpeg" alt="Research Icon" width="200" height="200" /> grabbing a hold of their destiny, doing their own scientific research and making important discoveries.


A recent account featured on<a href="https://www.propublica.org/article/muscular-dystrophy-patient-olympic-medalist-same-genetic-mutation"> This American Life</a> by<a href="http://www.propublica.org/site/author/david_epstein"> David Epstein</a>, a reporter with the non-profit news site Propublica and the author of The Sports Gene, is the latest in a series of stunning stories that highlight what is possible with the right amount of data, diligence and luck.
Epstein’s story looked at Jill Viles and<a href="http://www.gopriscilla.com/"> Priscilla Lopes-Schleip</a>, women who couldn’t seem more different – one a wheelchair-bound Iowan with wilted arms and legs, the other a Canadian Olympian known for her incredible musculature.
They both had mutations in the same gene that causes Dunnigan-type partial lipodystrophy a very rare genetic condition that results in the loss of subcutaneous fat in the limbs. But Jill had one other mutation in that same gene that triggered Emery-Dreifus, a rare type of muscular dystrophy. Epstein focuses on Jill’s incredible do-it-yourself approach to research, first identifying that she had lipodystrophy when she was only an undergraduate, and much later discovering that a connection between that condition and her rare form of muscular dystrophy.
And this story shares some of the same elements as several others we’ve seen recently, in which individuals faced with troubling symptoms and few answers, decide to dive into the science on their own and actually make meaningful discoveries.
One of the more striking stories is a wonderful article that ran last year in<a href="http://www.theatlantic.com/science/archive/2014/08/the-database-of-genetic-mutation/378792/"> The Atlantic</a> by Ed Yong. It focuses on Kim Goodsell, an endurance athlete who taught herself genetics to find out why she suffered from the rare genetic nerve disorder, Charcot-Marie Tooth disease, and another genetic disorder that affects her heart called arrhythmogenic right ventricular cardiomyopathy (ARVC). Smart and driven, Kim, who is not a scientist, was able to figure something out about the conditions that no one else had, that they were connected by mutations in the same gene, LMNA.


Finally there is the story about Eric Minikel and Sonia Vallabh, a married couple who changed their careers and became researchers after they learned that Sonia would likely develop a devastating and fatal neurodegenerative condition. The pair recently authored a paper making<a href="http://stm.sciencemag.org/content/8/322/322ra9.full"> important new findings</a> about prion disease.
There is some debate about whether stories like these represent a harbinger of things or simply edge case exceptions. The efforts featured each of these stories have yet to result in a cure, but each person featured is inspiring for what their efforts represent. Even if these are examples that few others could follow, they do point to the value of enlisting the patient in their own treatment.


As Eric Topol pointed out in Ed Yong’s story:
“People have been talking about empowering consumers since there was an Internet, but finally, we’ve reached a point where someone can delve into their condition beyond what the top physicians at the Mayo Clinic could.”

Citizen Science

As part of a collaboration with 23andMe, the personalized medicine company Celmatix is looking to dramatically improve the diagnosis and treatment of infertility.<img loading="lazy" decoding="async" class="alignright size-thumbnail wp-image-4040" src="https://blog-api.23andme.com/wp-content/uploads/2009/07/istock_000004280142xsmall-200x200.jpg" alt="istock_000004280142xsmall" width="200" height="200" />


Infertility affects a large portion of the population, with an estimated<a href="http://www.resolve.org/about/fast-facts-about-fertility.html"> one in eight couples</a> in the United States having difficulty conceiving. There are many reasons for that – couples waiting longer to have children, for instance – but by understanding the complex mix of environmental and genetic factors involved, medical professionals can better treat and diagnose the condition.
That’s what this collaboration is about. 


Over the last six years,<a href="http://celmatix.com/"> Celmatix</a> has discovered and annotated more than 5,200 different genetic biomarkers involved in fertility. By leveraging 23andMe’s massive genetic database – which includes input from nearly 200,000 men and women who have answered questions about fertility – Celmatix hopes to create tests that offer physicians better insight into the risks of infertility in their patients.


“The scale of the genetic data that 23andMe has amassed is unprecedented for the field of reproductive medicine,” said Piraye Yurttas Beim, Ph.D. the founder and CEO of Celmatix.


The collaboration may also help in the development of such things as early screening for the premature decline of ovarian function in women, which has implications not just on fertility but also general health. The effort is also inline with long term efforts by 23andMe.
“Fertility and women’s health have always been important to 23andMe and our research mission,” said Emily Drabant Conley, Ph.D., vice president of business development at 23andMe.  “We chose Celmatix as our partner for fertility research because they are the leader.”


23andMe has conducted related research. In 2015, researchers at the University of Cambridge, working with scientists here at 23andMe, found half a dozen new genetic variants associated with<a href="https://blog.23andme.com/23andme-research/new-findings-on-female-infertility/"> polycystic ovary syndrome</a>, the most common reproductive disorder in women and a common cause of infertility.


Over the years, 23andMe researchers have collected a steady stream of data on female fertility, male fertility and on couples.

Collaboration to Create Better Treatments for Infertility

Twins have long fascinated us as humans, so much so that twin stories are ingrained in the mythology of almost every culture.
Beyond folklore, the study of twins has also become the bedrock for much of what we know about the genetics of traits, diseases, and other conditions. 
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<div style="float: right; text-align: justified; width: 300px; background-color: #89c336; padding: 10px; margin-left: 10px;"><iframe loading="lazy" src="https://www.youtube.com/embed/IVug8r-hl5o" width="300" height="169" frameborder="0" allowfullscreen="allowfullscreen"></iframe></div>
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</code>For scientists, twins offer a ready-made test of nature and nurture, with their paired roles influencing everything from height to disease risk to intelligence. Looking at the similarities and differences shared between fraternal twins and identical twins has brought into sharp relief some of what can be explained through genetics and what can be explained from the environment. 
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</code>When we look at identical twins, we often are drawn more to their <a href="http://www.apa.org/monitor/2015/01/double-life.aspx" target="_blank" rel="noopener noreferrer">similarities than their differences</a>, but the differences can often be just as illuminating. 
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</code>Last year, a <a href="https://www.nature.com/ng/journal/v47/n7/full/ng.3285.html">meta-analysis</a> of more than 50 years of twin research—which included studies on more than 14.5 million pairs of twins—estimated that the influence of genes and the environment across all traits is about equal. 
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</code>Twins can be identical (monozygotic) or fraternal (dizygotic), but there are several other different types, including half-identical, mirror twins, and fraternal twins from different fathers (it happens). The rate of twin births has actually increased in the last 30 years, going from about 2 percent of all births to more than 3 percent.
Some of this may have to do with fertility treatment, and some might be related to women having children later in life. Older women are more likely to have twins than younger women.

Twins Seeing Double

If you have an opinion about genetic testing and the best way to return those results, the U.S. Food and Drug Administration (FDA) <img loading="lazy" decoding="async" class="alignright size-thumbnail wp-image-6586" src="https://blog-api.23andme.com/wp-content/uploads/2010/05/23andMe_Logo_blog-200x200.jpg" alt="23andMe_Logo_blog" width="200" height="200" />wants to hear it at a daylong workshop scheduled for March 2nd.how


The meeting offers the FDA a chance to get perspectives from the public and medical professionals on how best to convey genetic test results in a way that meets the needs of both patients and practitioners.
The meeting comes on the heels of the ambitious<a href="https://www.nih.gov/precision-medicine-initiative-cohort-program"> Precision Medicine Initiative</a>, announced during last year’s State of the Union address. Genetic testing and patient access and engagement are key components of the initiative.
As such the FDA is “considering new approaches in its regulation” of certain types of genetic testing, according to the<a href="https://www.gpo.gov/fdsys/pkg/FR-2016-01-14/html/2016-00540.htm"> Federal Register</a>. 
<div style="float: right; text-align: justified; width: 200px; background-color: #eee; padding: 15px; margin-left: 10px;">What: Patient and Medical Professional Perspectives on the Return of Genetic Test Results

When: March 2, 2016 from 8 a.m. to 4 p.m.

Where:<a href="https://www.fda.gov/AboutFDA/WorkingatFDA/BuildingsandFacilities/WhiteOakCampusInformation/ucm241740.htm" target="_blank" rel="noopener noreferrer"> FDA&#8217;s White Oak Campus</a> 
10903 New Hampshire Ave., Bldg. 31 
Conference Center, the Great Room (Rm. 1503) 
Silver Spring, MD 20993
For more information go here.
</div>

As part of the run-up to the meeting, the agency has offered up several case studies with different scenarios involving genetic testing. For instance, how to handle reporting on variants associated with different levels of risks for Alzheimer’s disease, or how to report on results that might include conflicting information or that have limited evidence.
The FDA wants to hear opinions on how best health care professionals should handle this kind of information.
You have three ways to participate:

<ol>
<li>Attend. People who want to attend and give their comments in person must register for the event, which has limited seating. The workshop is scheduled to begin at 8 a.m. ET March 2nd at the FDA’s<a href="https://www.fda.gov/AboutFDA/WorkingatFDA/BuildingsandFacilities/WhiteOakCampusInformation/ucm241740.htm"> White Oak Campus</a> in Silver Springs, Maryland.</li>
<li>Watch Webcast. The meeting will also be Webcast. Comments can be sent in the mail addressed to Division of Dockets Management (HFA-305), FDA, 5630 Fishers Lane, and Rm. 1061, Rockville, MD 20852.</li>
<li>Submit comments online. Comments can also be<a href="http://www.regulations.gov/#!docketDetail;D=FDA-2015-N-4809"> submitted online</a> by March 31st. All submissions, whether done through the mail or online must include reference to: “Docket No.  FDA-2015-N-4809 for `Patient and Medical Professional Perspectives on the Return of Genetic Test Results; Public Workshop; Request for Comments.’”</li>
</ol>

The FDA Wants To Hear Your Opinion

Get two smart people in a room and let them talk.
That’s the premise for astrophysicist Neil deGrasse Tyson’s show “StarTalk,” and it makes for thought-provoking conversations about <img loading="lazy" decoding="async" class="alignright size-thumbnail wp-image-23580" src="https://blog-api.23andme.com/wp-content/uploads/2016/02/neil-degrasse-tyson-and-genetics-guru-anne-wojcicki-on-a-future-without-disease-and-much-more-200x200.jpg" alt="neil-degrasse-tyson-and-genetics-guru-anne-wojcicki-on-a-future-without-disease-and-much-more" width="200" height="200" />science.


That’s what Neil got when he sat down with 23andMe’s CEO and co-founder Anne Wojcicki. As part of what Neil is calling his “Innovators” series, Neil started out with questions about why Anne started the company, and 23andMe’s mission.
And he wanted to know about her own hopes for future of 23andMe, but Neil also peppered the conversation with more fanciful and provocative questions about genetics.
Instead of a dystopian science fiction version of the future, Anne said that although there are some things to be concerned about, the possibilities for the future are much more hopeful.


“There’s a massive potential for good,” Anne told Neil.
Check out the conversation.
<script src="https://player.ooyala.com/iframe.js#pbid=3fa6999d63a34b9fbcf1cbbb67046fe6&#038;ec=R0dW9qMDE6XQB6-x1QPGD6CMjXfqpVj2"></script>

Smart Talk

In a <a href="https://www.nature.com/ncomms/2016/160202/ncomms10448/full/ncomms10448.html" target="_blank" rel="noopener noreferrer">new study </a>published today in Nature Communications, 23andMe researchers identified 15 genetic variants associated with being a morning person, including four never-before-connected to sleep cycles and associations like BMI and depression.
<img loading="lazy" decoding="async" class="alignright size-larger wp-image-23367" src="http://35.88.189.111/wp-content/uploads/2015/12/11032015_morningness_brandUpdate-1-193x880.png" alt="" width="193" height="880" srcset="https://blogcms.23andme.com/wp-content/uploads/2015/12/11032015_morningness_brandUpdate-1-193x880.png 193w, https://blogcms.23andme.com/wp-content/uploads/2015/12/11032015_morningness_brandUpdate-1-66x300.png 66w, https://blogcms.23andme.com/wp-content/uploads/2015/12/11032015_morningness_brandUpdate-1-768x3501.png 768w, https://blogcms.23andme.com/wp-content/uploads/2015/12/11032015_morningness_brandUpdate-1-259x1180.png 259w, https://blogcms.23andme.com/wp-content/uploads/2015/12/11032015_morningness_brandUpdate-1.png 1500w" sizes="auto, (max-width: 193px) 100vw, 193px" />
<h2>Circadian Rhythm Genes</h2>
“Some circadian rhythm genes we identified have been studied in model organisms, but much less so in humans,” said David Hinds, Ph. D., a Principal Scientist and Statistical Geneticist at 23andMe, who was a co-author on the paper. We also identified new genes that have not previously been associated with sleep behavior.”
Among the genetic variants in this study, researchers found seven in or near genes already known to play a biological role in circadian rhythms. Four other variants identified are in or near genes that could plausibly be related to circadian rhythm, and the remaining four variants are more of a mystery in their role in human sleep cycles.
<h2>Related Phenotypes</h2>
Analyzing the phenotypic data, the researchers also examined associations between morning habits and conditions such as body mass index, insomnia, depression, and sleep duration.
They found that a morning person is much less likely to have insomnia, less likely to require eight hours of sleep, and less likely to suffer from depression than individuals who reported being “night owls.” Considering the effect of age and sex, morning persons are also more likely to have lower BMI, according to the research. The researchers also found that morning persons were less likely to be on the extreme ends of body mass index, meaning they were less likely to be obese and less likely to be underweight.
While this does not imply causation, some associations may warrant a deeper dive into biology. For instance, several new genetic associations were found in the FTO gene, which is associated with obesity.
<h2>Night Owl or Morning Person</h2>
Circadian rhythms are sleep and wake cycles in a 24-hour day. The cycle is triggered by changes in light stimulation. While scientists have long known that one&#8217;s genetics can influence one&#8217;s circadian rhythm, they have yet to piece together the full picture.
However, understanding why someone is more likely to be a morning person or a “night owl” continues to perplex researchers. By learning more, researchers may better understand certain health conditions associated with those differences,   such as depression, obesity, and insomnia.
23andMe’s genome-wide association study examined data from more than 89,000 customers who consented to research and answered questions about their sleep cycles. Using imputation—statistical methods to infer unobserved genotypes—the researchers were able to examine approximately eight million genetic variants, giving them a much more robust picture of the genetic influence on sleep cycles.
<h2>Morningness</h2>
On the eve of 23andMe&#8217;s paper&#8217;s publication, a team at the University of Exeter Medical School in the UK completed a similar study.
The researchers there used data from 119,000 individuals in the <a href="http://www.ukbiobank.ac.uk/about-biobank-uk/" target="_blank" rel="noopener noreferrer">UK Biobank</a> study and coordinating with 23andMe&#8217;s researchers, they were able to replicate 13 of the 16 variants they found associated with being a morning person or &#8220;morningness&#8221; in that data, including finding variants in genes associated with BMI and circadian rhythms. A preprint of the team&#8217;s paper, which is in review for publication, is posted here.
Although not part of the research in this paper, 23andMe scientists looked at this data in another way, precisely how &#8220;morningness&#8221; distributes itself geographically in the United States. Using random sub-sampling, our scientists looked at the proportion of morning people by state among customers in the US who consented to research.
The map below shows clustering along time zones – especially among the states in the mountain time zone – Colorado, New Mexico, Wyoming, and Montana.
According to 23andMe scientist Kasia Bryc, who did the analysis, some of the states with the highest proportion of morning people also tend to have older populations. However, there are many anomalies, making it difficult to draw conclusions. At the same time, the map illustrates that, as with most traits, it&#8217;s not just genetics that plays a role.
What do you think explains this distribution? <img loading="lazy" decoding="async" class="aligncenter wp-image-23472 size-large" src="http://35.88.189.111/wp-content/uploads/2016/01/01152016_morningMap_social-1024x532.png" alt="" width="1024" height="532" srcset="https://blogcms.23andme.com/wp-content/uploads/2016/01/01152016_morningMap_social-1024x532.png 1024w, https://blogcms.23andme.com/wp-content/uploads/2016/01/01152016_morningMap_social-300x156.png 300w, https://blogcms.23andme.com/wp-content/uploads/2016/01/01152016_morningMap_social-768x399.png 768w, https://blogcms.23andme.com/wp-content/uploads/2016/01/01152016_morningMap_social-880x457.png 880w, https://blogcms.23andme.com/wp-content/uploads/2016/01/01152016_morningMap_social-1180x613.png 1180w, https://blogcms.23andme.com/wp-content/uploads/2016/01/01152016_morningMap_social.png 1500w" sizes="auto, (max-width: 1024px) 100vw, 1024px" />
The paper appears in the journal <a href="http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1006125" target="_blank" rel="noopener noreferrer">PLoS Genetics</a>.

New genetic variants found to influence likelihood of being a morning person

Total strangers, John and Rhonda have one thing in common, the same father.<img loading="lazy" decoding="async" class="alignright wp-image-23484 size-medium" src="https://blog-api.23andme.com/wp-content/uploads/2016/01/JR-quote-300x169.jpg" alt="J$R quote" width="300" height="169" srcset="https://blogcms.23andme.com/wp-content/uploads/2016/01/JR-quote-300x169.jpg 300w, https://blogcms.23andme.com/wp-content/uploads/2016/01/JR-quote-768x432.jpg 768w, https://blogcms.23andme.com/wp-content/uploads/2016/01/JR-quote-880x495.jpg 880w, https://blogcms.23andme.com/wp-content/uploads/2016/01/JR-quote-980x553.jpg 980w, https://blogcms.23andme.com/wp-content/uploads/2016/01/JR-quote.jpg 984w" sizes="auto, (max-width: 300px) 100vw, 300px" />


The two made that discovery earlier this year after using 23andMe.


“Nobody knew about John,” said Rhonda, a 55 year-old marketer in Buffalo New York.


For John, recently retired and 67 who also lives in the Buffalo area, DNA testing was the only way he would have ever found Rhonda and information about his biological father. For both of them the test helped lead them to clues about their father and a tangled history of multiple families and an ongoing search for siblings spread out through generations and geography.
“I now have a printed family tree that  takes three trees to show and is  so long, it covers the top of two long tables,” said John. “(Testing has) been a positive experience for me and a healing experience for the family. I&#8217;ve been welcomed with open arms.”


Being orphaned, along with his half brother, from his single mom when he was just 10 had been so traumatic for John, that he blanked out all the memory of his childhood. He couldn’t even remember his mother’s face until a few years ago when he saw a photo of her for the first time. That had been out of sheer luck, after a mutual acquaintance connected him to his cousin and elderly aunt. John believes it may have been more than luck with a little help from his mother, watching from above.
It was his aunt and cousins who had the photo and tidbits about his mother. John and his family enjoyed a series of reunions in the US and in Italy over the past 5 years. His aunt also shared with John the one bit of information she had about his biological father, his father’s first name.
<div id="attachment_23482" style="width: 210px" class="wp-caption alignright"><img loading="lazy" decoding="async" aria-describedby="caption-attachment-23482" class="size-thumbnail wp-image-23482" src="https://blog-api.23andme.com/wp-content/uploads/2016/01/John-Vitale-200x200.jpg" alt="John Vitale" width="200" height="200" />John Vitale</div>
“There is no way I could have identified the family on my father&#8217;s side,” he said. “All I had to go on was his name was Marvin, and I only learned that a couple of years ago.”


But for both John and Rhonda using 23andMe to explore their ancestry changed not just what they knew about their families and their background, but their understanding about themselves.
John had thought he was Italian, but was “shocked” to learn he was half Ashkenazi Jew on his father’s side.


“I knew nothing about my father, I assumed he was Italian,” said John. “My mother&#8217;s family is Italian with roots in Sicily and Milan.   I was raised Catholic.”
Learning about his Jewish ancestry, didn’t change his beliefs, but it did change his perceptions.


“It has made me more sensitive and curious of the Jewish faith,” he said.


For Rhonda, who was raised by a Jewish mother, learning about about her biological mother’s Catholic background put certain things about herself in context. It also raised a lot of “nature versus nurture issues” for her.


“I grew up as an only child, in a family that I was very different from,” she said. “I look nothing like, or act nothing like, my adopted mother or father.”


And then there was the connection she made using 23andMe to her biological family for the first time – not just to John, but also to a full sister named Trisha.
That connection with her sister was so strong that Rhonda wonders if there’s a chance that they might actually be twins separated and adopted out to different families.


“When I met Trisha, it felt like I was talking to myself,” Rhonda said. “The similarities were astounding.”


23andMe also helped Rhonda connect with her oldest living half-sibling, who is unrelated to John. She was one of the 2 children born to her mother when her mother was in an internment camp in Germany. It was that woman, Danuta, who gave Rhonda much of what she knows about her mother, including her mother’s history with Marvin and the other children she bore him.
<div id="attachment_23483" style="width: 210px" class="wp-caption alignright"><img loading="lazy" decoding="async" aria-describedby="caption-attachment-23483" class="size-thumbnail wp-image-23483" src="https://blog-api.23andme.com/wp-content/uploads/2016/01/rhoried-pic-200x200.jpg" alt="Rhonda Ried" width="200" height="200" />Rhonda Ried</div>
All of Rhonda’s full siblings were adopted by other families, she said. At least two of whom she’s connected with through 23andMe. Rhonda discovered she has 5 full siblings and 6 half siblings, including John. And there could be more, she said.
Now both Rhonda and John are hoping that they will be able to connect with other siblings. They are aware of two sisters in Arizona.


“We are becoming acquainted with members of the family living around the country,” John said.


They have scheduled a virtual family reunion on Skype in a few weeks, but their search continues.


“I fully expect we’ll find others,” said John. “We’ll just keep looking.”

Nobody Knew

Researchers often say it’s their love of science that drives their work, but for Eric Minikel and Sonia <img loading="lazy" decoding="async" class="alignright size-full wp-image-23490" src="https://blog-api.23andme.com/wp-content/uploads/2016/01/Eric-Sonia-in-the-Lab.jpg" alt="Eric &amp; Sonia in the Lab" width="261" height="213" />Vallabh it’s their love that propels the science.
The married couple – both are researchers at the Broad Institute and are completing their doctorates at Harvard Medical School – helped to co-author <a href="http://stm.sciencemag.org/content/8/322/322ra9.full" target="_blank" rel="noopener noreferrer">a new paper</a> looking at the genetic risk for developing prion disease, a rare but devastating condition that hits the nervous system, impairs brain function, triggers other neurodegenerative symptoms such as memory loss and insomnia, and ultimately causes death. It’s triggered when a protein misfolds causing clumping in brain tissue, typically manifesting itself around the age of 50.
<h2>It&#8217;s Personal</h2>
For Eric and Sonia this research is personal, as Eric movingly writes in <a href="http://www.cureffi.org/2016/01/20/does-this-mean-ill-definitely-get-the-disease/" target="_blank" rel="noopener noreferrer">this blog post</a>.
About five years ago, not long after they married, their lives took a sharp turn when Sonia’s mother died at 52. It was only after her mother passed away that Sonia and Eric learned about what killed her – Fatal Familial Insomnia, a form of prion disease. Soon thereafter, Sonia learned that she inherited a genetic mutation, putting her at a very high risk for the disease.
In response, first Sonia, who’d recently graduated from law school at Harvard, and then Eric, a city planner and software engineer, made career changes, dedicating their lives to finding a cure for prion disease. They started working at a lab at Massachusetts General Hospital, took night courses and eventually were accepted at Harvard Medical School. They now work in the Stuart L. Schreiber Research Laboratory at the Broad Institute of MIT and Harvard.
<div id="attachment_23491" style="width: 230px" class="wp-caption alignright"><img loading="lazy" decoding="async" aria-describedby="caption-attachment-23491" class="wp-image-23491 size-full" src="https://blog-api.23andme.com/wp-content/uploads/2016/01/Sonia-in-the-Lab.jpg" alt="Sonia in the Lab" width="220" height="209" />Sonia working in the lab.</div>
Even before this paper they made an impact. A few years ago, the couple formed the non-profit<a href="http://www.prionalliance.org/"> Prion Alliance</a> and Eric started the blog<a href="http://www.cureffi.org/"> CureFFI</a>, which is a great resource for information about research into prion disease. It also catalogues his education in the science and what motivates him.
<h2>Recognition for their Work and Story</h2>
Their story has been featured in both the<a href="http://www.theatlantic.com/health/archive/2015/02/insomnia-that-kills/384841/"> Atlantic</a> and the<a href="https://www.newyorker.com/books/page-turner/a-prion-love-story"> New Yorker</a>. A joint presentation they did at the American Society of Human Genetics focused on citizen science and<a href="https://www.youtube.com/watch?v=d9d_8SzXfIc"> crowdsourcing for scientific research</a>.
More recently, Eric<a href="http://www.cell.com/ajhg/abstract/S0002-9297%2814%2900386-3"> developed a statistical method</a> that refuted previous studies suggesting that in families with inherited prion disease, the disease will manifest itself as much as 14 years earlier with each generation. If true that would have been devastating for Sonia, who turned 31 in 2015. However, Eric’s findings also highlight problems with research into other rare diseases, which can suffer from a lack of data or selection bias because the data comes from within the disease communities they study.
The research for this paper – which draws in part from data provided by 23andMe and Exome Aggregation Consortium data from the Broad – is important because it changes assumptions about the risks associated with some of the more than 60 mutations in the PRNP gene that are thought to confer risk for prion disease. In  another recently published paper, Harvard&#8217;s Robert Green points out that Eric and Sonia&#8217;s work doesn&#8217;t just shed light on prion; it also highlights the power of sharing genetic data:
&#8220;The story of this research stands as a testament to the generosity of unrequited data sharing from thousands of individuals and scientists around the globe and to the unflinching devotion of a young couple to alter their seemingly unalterable genetic destiny,&#8221; Green writes.
<h2>Real Progress</h2>
The study began with the observation that variants in the PRNP gene that have been reported to cause prion disease are at least 30 times more common than expected in the general population. Up until now, many doctors have assumed that all those mutations were associated with a 100 percent risk of developing the disease. However, if all of these mutations were “completely penetrant,” or 100 percent disease-causing, then the number of people developing the disease each year would have to be much higher than what is seen in clinics worldwide. This discrepancy suggested to the researchers that some of these variants could have “incomplete penetrance” or may even have no impact on the disease risk.<img loading="lazy" decoding="async" class="alignright size-medium wp-image-23502" src="https://blog-api.23andme.com/wp-content/uploads/2016/01/eric-sonia-in-lab-300x177.jpg" alt="eric-sonia-in-lab" width="300" height="177" srcset="https://blogcms.23andme.com/wp-content/uploads/2016/01/eric-sonia-in-lab-300x177.jpg 300w, https://blogcms.23andme.com/wp-content/uploads/2016/01/eric-sonia-in-lab-768x453.jpg 768w, https://blogcms.23andme.com/wp-content/uploads/2016/01/eric-sonia-in-lab.jpg 800w" sizes="auto, (max-width: 300px) 100vw, 300px" />
By comparing the frequency of individual variants in prion disease patients versus the general population, the team found that the variants previously reported to cause prion disease aren’t all created equal — they actually form a spectrum of risk. At one end, some mutations previously reported as disease-causing appear benign, meaning that they do not increase the risk of prion disease above the baseline risk in the general population.
<h2>Variants with Different Risk</h2>
On the other end, some mutations really do convey a very high risk, upwards of 80-to-90 percent, of developing disease in one’s lifetime. In between, some variants appear to convey an intermediate lifetime risk of, for example, 0.1 or 10 percent. Then, there were some variants for which the data was insufficient to draw conclusions.
According to the researchers, this is great news for some individuals who carry variants that now appear to be low-risk.
“Through our relationship in the patient community, we have met people with several of the mutations that we now believe are low-risk or benign. Some of those people had been told they had a very high risk of disease, so our work changes their prognosis,” said Eric.
Unfortunately, Sonia’s mutation, D178N, isn’t one of those that is low-risk. The new research confirms that the mutation she carries—along with mutations that many others carry—confers a near 100 percent risk for developing prion disease.
“Our work doesn&#8217;t change the prognosis for most patients with genetic prion disease,” said Eric. “Only a minority of them.”
Although it doesn’t directly change Sonia’s prognosis, the new study may help develop drugs to treat prion disease. The study found that a few reduce the prion protein&#8217;s function among the benign mutations. Because carriers of these so-called &#8220;loss-of-function&#8221; mutations are apparently healthy, it suggests that developing drugs that work against the protein may be safe. Eric and Sonia are now working on developing molecules to do just that, and they can move in that direction more confidently.
<h2>Love and Science</h2>
In the context of prion disease, this study positively impacts the prognosis for a few hundred individuals worldwide while providing validation for a therapeutic strategy that may offer hope more broadly to patients and families affected by prion disease.
The researchers said that, more generally, the study also highlights the value of large reference datasets like 23andMe’s and Broad&#8217;s.
For this study, researchers used exome data from 60,000 people collected by the Broad Institute from a large international consortium and genotypic data from more than 530,000 23andMe customers who consented to research. Excitingly, as datasets of this size continue to grow, so will their power to expand and refine our understanding of human disease.
In the couple profile that appeared in the New Yorker in 2014, the writer quotes from an email he received from Sonia trying to describe her relationship with Eric.
“I thought when I married him that I could never love anyone more than I did that day. But I was wrong,” she said. “We are in a new dimension of partnership now, and I am more in love and, frankly, more in awe of him with every day we spend together. His brain is outstandingly powerful, and I see things I would never have known he was capable of in any other way. He was meant to do this work, and the world will be better for it.”
Love might not conquer all, but Eric and Sonia’s work points to what it can do when fueling the work of two brilliant minds.

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