This month, 23andMe published a new article in PLoS One entitled “<a href="http://www.plosone.org/article/info:doi%2F10.1371%2Fjournal.pone.0034267">Cryptic Distant Relatives are Common in both Isolated and Cosmopolitan Samples</a>.&#8221; Authored by former 23andMe scientists, Brenna Henn and Lawrence Hon, along with current 23andMe scientists and 23andMe advisor, Itsik Pe’er, of Columbia University, the article describes the nuts and bolts of the method behind our innovative Relative Finder tool. In this post, Brenna discusses what the findings mean for our notion of “relatives” and explores the many special features of the 23andMe customer database.
By Brenna Henn
You probably know how many siblings you have or the number of first cousins. But do you know how many 2nd cousins you have? Does 38 sound reasonable? What about the number of 3rd, 4th, or 5th cousins?
The answer may surprise you.
<h6>What&#8217;s a Fourth Cousin?</h6>
Under a simple model where a family has 2-3 children, you would have 190 third cousins, 940 fourth cousins, and a whopping 4,700 fifth cousins.
Going back to 8th cousins (or 9 generations back to a common ancestor), the model we developed predicts you would have over half a million 8th cousins!
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Now, this model is a simplification because some families have a dozen children and some have none; but this model does help illustrate just how many potential distant cousins are out there.
<h6>Relative Finder Tool</h6>
Finding a relative in the 23andMe database, however, rests on two other important conditions. First, the relative has to be a 23andMe customer. Second, you and the relative need to share a long identical segment of DNA. The more distant a pair of cousins, the less identical DNA they share. Very small fragments of DNA can be hard to detect with our algorithm.
So although you might have thousands of 6th cousins, we think we can only detect about 4% of them with 23andMe’s current technology.
Our detection success is much higher for more closely related cousins, though — we can detect about 46% of 4th cousin pairs and 90% of 3rd cousin pairs.
<h6>Connections Among Those with Ashkenazi Ancestry</h6>
Our ability to detect a person’s distant cousins is also influenced by the ancestry of the individual. If you are Ashkenazi Jewish, you may have noticed that 23andMe’s Relative Finder feature shows you over a thousand cousins.
This is because Ashkenazi Jews are more closely related to each other than a random sample of European-Americans. Over the past several hundred years, a cultural tendency to choose marriage partners of the same ethnicity (also known as endogamy) means that Ashkenazi individuals are more likely to share the same ancestors.
In fact, we estimate that any two randomly chosen individuals who identify as Ashkenazi is on average the genomic equivalent of 4th-5th cousins because they share many recent common ancestors.
This phenomenon doesn’t just occur in the Ashkenazim.
<h6>Looking at Different Populations</h6>
We looked at 121 populations, many from the 23andMe customer database. Pairs of individuals in Iceland, Finland, or South Africa are more closely related than pairs of individuals from Italy or Japan.
<div style="float: right; text-align: left; width: 200px; padding: 10px; margin-left: 15px; border: 1px solid black;"><img loading="lazy" decoding="async" class="alignright size-full wp-image-12163" style="float: left; margin-right: 5px;" title="small_23andMe_logo" src="https://blog-api.23andme.com/wp-content/uploads/2012/04/JRBgdIBXKIeVIdETJrxYIw_ttam_logo.jpg" alt="" width="24" height="40" />Connect with 23andMe members who share DNA and ancestors. Not yet a 23andMe customer? <a href="https://www.23andme.com/store">Visit our store</a> or <a href="https://www.23andme.com">learn more</a>!</div>
In our analyses, we also looked at DNA data for over 5,000 individuals with just European ancestry in the 23andMe database. The DNA indicated that in this sample there are over 5,000 3rd cousin pairs and 30,000 4th cousin pairs. This result is important beyond thinking about genealogy.
It means that large disease association studies that sample thousands of individuals will have many pairs of distant cousins in the dataset. By identifying cryptic (or non-obvious) relatives in databases, researchers can see if certain disease mutations occur more often in different extended families.

Brenna Henn

The method behind the Relative Finder tool

<img loading="lazy" decoding="async" class="aligncenter wp-image-12249 size-full" style="border: 1px solid #ccc;" title="PDgene" src="http://35.88.189.111/wp-content/uploads/2012/04/PDgene.png" alt="" width="770" height="700" srcset="https://blogcms.23andme.com/wp-content/uploads/2012/04/PDgene.png 770w, https://blogcms.23andme.com/wp-content/uploads/2012/04/PDgene-300x273.png 300w, https://blogcms.23andme.com/wp-content/uploads/2012/04/PDgene-768x698.png 768w" sizes="auto, (max-width: 770px) 100vw, 770px" />
By Nick Eriksson
At 23andMe, we read a lot of papers so that we can bring our customers the latest information about their genetics. This is a tall task: there were nearly a million papers published in the biomedical and life sciences in the year 2011 alone. That’s why we’re appreciative when others wade through all of this data.
We’re particularly excited about a recent paper in PLoS Genetics &#8212; “<a href="http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1002548">Comprehensive Research Synopsis and Systematic Meta-Analyses in Parkinson&#8217;s Disease Genetics: The PDGene Database</a>” &#8212; for several reasons. Not only is April Parkinson’s Disease Awareness Month but we’re proud to say that 23andMe contributed to this new <a href="http://www.pdgene.org">database</a> with the help of the many active participants in our Parkinson’s disease research community.
The authors of the paper looked at over 27,000 articles published on Parkinson’s disease, including over 800 genetic association studies of the disease (such as the <a href="http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1002141">23andMe study</a> published last summer). They gathered data from over 3,000 different genetic polymorphisms from these studies in order to create the most comprehensive synopsis of Parkinson’s disease genetic research to date.
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If you have Parkinson&#8217;s or know someone who does, <a href="https://www.23andme.com/pd">spread the word and get involved</a> in our groundbreaking research.
Don&#8217;t have Parkinson&#8217;s? You can still help by <a href="https://www.23andme.com/store">becoming a 23andMe customer</a> and filling out surveys!
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Scientists are trained to look for novelty. Thus, the task of summarizing other people’s work often can seem rather thankless. This paper, however, shows the importance of taking a second look at published data. The authors confirmed the associations between 11 genes and Parkinson’s disease that had previously been reported. Importantly, they also found a new genetic association near a gene called ITGA8, moving us another step closer in figuring out how genetics affects Parkinson’s disease risk.

Nick Eriksson

PDGene Enters the Scene for Parkinson’s Research

<img loading="lazy" decoding="async" class="aligncenter wp-image-12215 size-full" title="marsalis-musical-ancestor" src="http://35.88.189.111/wp-content/uploads/2012/04/marsalis-musical-ancestor.png" alt="" width="504" height="280" srcset="https://blogcms.23andme.com/wp-content/uploads/2012/04/marsalis-musical-ancestor.png 504w, https://blogcms.23andme.com/wp-content/uploads/2012/04/marsalis-musical-ancestor-300x167.png 300w" sizes="auto, (max-width: 504px) 100vw, 504px" />&#8220;Musical Royalty&#8221;: <a href="http://video.pbs.org/video/2206762934">Watch the video</a> from the PBS series Finding Your Roots with Henry Louis Gates, Jr., as he speaks with Branford Marsalis about his relative Wellman Braud, a pioneering jazz bassist.
Just as jazz greats Harry Connick Jr. and Branford Marsalis wondered, in the first segment of the PBS series Finding Your Roots, whether they had musical ancestors, you too might wonder where you got your penchant for painting or your bright blue eyes.
Many traits, as you might imagine, are complicated – is someone a musician because of innate, and possibly genetic ability, or because of her environment? Are you outgoing or shy because of your genes, or because of how you grew up? In most cases it is likely a combination of both, but that may make it even more interesting to learn that your ancestors shared certain qualities you see in yourself, whether it be a special talent or a streak of stubbornness.
<h6>Family Traits</h6>
For some traits, it can be easy to see a resemblance. Many of us have gazed at old, faded photographs of our parents or grandparents (or more distant relatives, if we’re lucky!) in their younger years and marveled at how we can see ourselves in them. The connection can be something obvious, like wild unruly hair or a distinctive shape of the nose, or it can be as subtle as a smile.
Because of genetic discoveries, you can trace a few such traits through your DNA. Those bright blue eyes could be due to specific factors located in genes responsible for pigment, passed down through generations. Or, if you’re Asian, you might look around the table at family holidays and see the pink-flushed cheeks that accompany a glass of wine – also a trait known to have a genetic basis. Does your mother’s father have male-pattern baldness?
If you’re a man, chances are that you’ll inherit this trait as well.
<h6>Perfect Pitch</h6>
<img loading="lazy" decoding="async" class="alignright size-medium wp-image-12209" title="EyeColor" src="https://blog-api.23andme.com/wp-content/uploads/2012/04/EyeColor-300x116.png" alt="" width="300" height="116" srcset="https://blogcms.23andme.com/wp-content/uploads/2012/04/EyeColor-300x116.png 300w, https://blogcms.23andme.com/wp-content/uploads/2012/04/EyeColor.png 516w" sizes="auto, (max-width: 300px) 100vw, 300px" />If they carry one particular genetic variant, two individuals with brown eyes can have children with almost any color eyes.
Research on the specific musical ability called “perfect pitch” suggests that this ability to recognize and produce musical tones is the combination of innate potential and early training. But we don’t yet know which genes are involved.
Indeed, no one has discovered much about the genetics of traits like artistic ability or personality. Why hasn’t anyone figured these out yet? Researchers have certainly searched for genetic contributions to handedness, personality, and <a href="http://35.88.189.111/articles/rhythm-and-musical-traits">musical ability.</a>
But it may be that the genetic models we assumed in those studies were too simple.
<h6>Genetic Models</h6>
In one common type of genetic study, researchers compare two groups of people — those with a trait (say, perfect pitch) and those without. They step through a million or more genetic “markers” or positions throughout the genome, and ask at each step, “Do the people with perfect pitch have more of one version of this DNA marker than do the people without perfect pitch?”
This approach works well if many of the people with perfect pitch have the same genetic variant, and that variant influences the trait strongly. This doesn’t seem to be the case for many traits, however.
<h6>Bigger Studies</h6>
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23andMe customers can see what traits they and a potential partner might pass on to their children.
Not yet a customer? <a href="https://www.23andme.com/store">Visit our store</a> or learn more about the <a href="https://www.23andme.com">Personal Genome Service ®</a>.
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Two things will help researchers discover the genetic factors behind those traits we see shared in families. First, studies that include a very large number of people with and without a given trait will help us find common genetic factors that have even a small influence on the trait.
By involving tens of thousands of people in studies, researchers have recently discovered genetic variants that influence freckling, sneezing in bright sunlight, and whether or not someone has a sweet tooth.
<h6>More Genetic Data</h6>
Second, a trait such as the love of vinegar and lemons that you share with your cousin may be influenced by genetic variants that are unique to your extended family. In that case full genome sequencing – that is, examination of all 3 billion positions in the genomes of a few family members – would be needed to get to the bottom of the family mystery.
DNA can tell us a lot about our ancestors and where we came from, and it turns out that it can also tell us a bit about why we’re the way we are. Perhaps that trait you share with someone in your family tree comes from a little shared DNA.

23andMe Blog

23andMe Blog Team

Ancestral Traits

On his first Space Shuttle mission, Rich Clifford whispered a little prayer.
<img loading="lazy" decoding="async" class="aligncenter wp-image-12186 size-full" src="http://35.88.189.111/wp-content/uploads/2012/04/rich-portrait1.jpg" alt="" width="533" height="434" srcset="https://blogcms.23andme.com/wp-content/uploads/2012/04/rich-portrait1.jpg 533w, https://blogcms.23andme.com/wp-content/uploads/2012/04/rich-portrait1-300x244.jpg 300w" sizes="auto, (max-width: 533px) 100vw, 533px" />“Please Lord let something go wrong so that I can fix it,” he recalls with a smile.
But on the launch pad, strapped into the Shuttle with its two massive solid rocket boosters primed for ignition, Rich had second thoughts.
“I said to myself: ‘Lord, scratch that earlier request.’”
Strange as his whispered prayer sounds now, it wasn’t so odd for an astronaut – someone with “The Right Stuff” – to want to be tested.
As a West Point cadet, then as an experimental test pilot, then as a Master Army Aviator and then as a NASA mission specialist, Rich spent his life facing huge challenges and overcoming them.
But for almost two decades, since the time just before his last mission into space, Rich has quietly faced the biggest challenge of his life: Parkinson’s disease.
His story and his fight against Parkinson’s is the subject of Zach Jankovic’s soon to be completed documentary, <a href="http://theastronautssecret.com/" target="_blank" rel="noopener noreferrer">“The Astronaut’s Secret.”</a>
On a recent visit to 23andMe, Rich said there’s a reason he’s been talking about that secret now. He has a message for others with Parkinson’s: “
“Don&#8217;t let it drive what you do. You are in charge of your future.”
Rich’s comments came earlier this year when he and Zach, as well as a small crew visited 23andMe to shoot some footage for the film and get a run down of some of the new research we’re doing.
They also sat down and spoke with our CEO Anne Wojcicki about the 23andMe’s Parkinson’s Research Community.
For Rich, 23andMe’s approach of using consumer-driven research is particularly appealing because it empowers people. It gives them a role in research, speeds the process of discovery and gives people back information about themselves. 23andMe created this novel approach to enlist people as partners in research, said Anne.
In the case of Parkinson’s our efforts have already yielded some promising results, she said. Last year we published a research paper detailing our <a href="https://www.23andme.com/about/press/sgk1/" target="_blank" rel="noopener noreferrer">discovery of two novel genetic associations</a> with Parkinson’s. And 23andMe also identified a <a href="https://www.23andme.com/about/press/sgk1/" target="_blank" rel="noopener noreferrer">genetic factor in a gene called SGK1 that may protect against the disease</a>.
We’ve partnered with <a href="http://www.scripps.edu/">The Scripps Research Institute</a> to further study the connection between SGK1 and a Parkinson’s to determine if indeed this variant is protective against the disease. What’s compelling about this finding, Anne said in the interview, is that it was made possible because we  found people in our database who have a high risk variant for Parkinson’s but never developed the disease. By comparing these people with those who did develop Parkinson’s our researchers were able to discover this potentially protective nature of SGK1. Beyond the potential of this discovery, Rich said he sees great promise in using genetic analysis to better diagnose Parkinson’s. The sooner a patient can be diagnosed the sooner they can start treatment and the better chance they’ll have at managing the disease. This is particularly relevant for Rich, who was fortunate enough get an early diagnosis, while with NASA. It didn’t stop him from flying on his third mission in 1996, where he made the first
The sooner a patient can be diagnosed the sooner they can start treatment and the better chance they’ll have at managing the disease. This is particularly relevant for Rich, who was fortunate enough get an early diagnosis, while with NASA. It didn’t stop him from flying on his third mission in 1996, where he made the first space walk in more than two decades with a fellow astronaut.  The diagnosis also didn’t stop him from spending 15 years working in a high profile job at Boeing after he left NASA and retired from the military. It was Zach’s dad, Dr. Joseph Jankovic, director of the Parkinson&#8217;s Disease Center and Movement Disorders Clinic at Baylor College of Medicine in Houston, who first diagnosed Rich.
But Rich said even though he is optimistic about the work on Parkinson’s and hasn’t let the disease slow him down, it hasn’t been easy. The first hint he had of the disease was when he noticed that his arm didn’t swing in the normal way when he was walking. When he got the diagnosis he told his doctors, “OK so fix it.” He admits, that at first, he was in denial about the disease. But then, like with every other challenged he’s faced in his life, Rich met it
When he got the diagnosis he told his doctors, “OK so fix it.” He admits, that at first, he was in denial about the disease. But then, like with every other challenged he’s faced in his life, Rich met it head on. He wanted to continue his work with NASA and the doctors supported him, he said. Now he wants to share his story in the hopes of inspiring others with Parkinson’s to understand that a diagnosis doesn’t mean that they won’t be able to continue to go after their dreams.
But to do that people with Parkinson’s have to take charge, learn what they can about the disease, <a href="https://www.23andme.com/pd">participate in research</a> and not give up. One of the things that resonated with Rich about what 23andMe does is that it gives people the tools to do that. The work could also lead to early detection for people facing Parkinson&#8217;s, and the sooner someone knows they’re at risk the sooner they can do something about it.
“Knowledge is power,” he said.

An Astronaut Tells His Secret

By Ann Turner, M.D.
Many members of my extended family have inherited a mutation responsible for hearing impairment.   The loss is detectable in childhood and progresses gradually over the years. I began wearing hearing aids forty years ago, when I was thirty.
<h6>A Search</h6>
We have participated in several genetic studies over the years, but the cause has not been found yet. I decided to see how far I could get by testing cousins with and without the hearing impairment. With testing could I at least identify a chromosomal region shared by just the relatives with the condition?
<div id="attachment_22394" style="width: 297px" class="wp-caption alignright"><img loading="lazy" decoding="async" aria-describedby="caption-attachment-22394" class="size-medium wp-image-22394" src="https://blog-api.23andme.com/wp-content/uploads/2015/04/Ann_cropped_modified-287x300.jpg" alt="" width="287" height="300" srcset="https://blogcms.23andme.com/wp-content/uploads/2015/04/Ann_cropped_modified-287x300.jpg 287w, https://blogcms.23andme.com/wp-content/uploads/2015/04/Ann_cropped_modified.jpg 355w" sizes="auto, (max-width: 287px) 100vw, 287px" />Dr. Ann Turner, MD</div>
I began with myself and two cousins in 2007 when autosomal testing was first offered at deCODEme (at a cost of nearly $1000) and continued adding cousins and even spouses as the prices dropped more and more at 23andMe.
Using traditional genealogical techniques, we were able to track the trait back through almost 200 years to John Riley (born about 1813 in Stafford County, Virginia) or his wife Mary Ellen Bigger (born about 1810 in County Antrim, Ireland).
<h6>Hearing Loss</h6>
We knew from memories of older family members that one of their children, Eliza Jane, was very hard of hearing. A letter written in 1893 by Eliza Jane to her sister Allie survives, wherein she asks:
“Does your hearing fail you anny? [sic] George is quite bad.”
Her brother George was 47 at the time, and Allie was 40. Clearly they were anticipating a condition that “ran in the family,” even before the term genetics was coined. As it turned out, Allie was not affected, but another brother, James, had a more complicated history.
James’ hearing difficulties are documented in some Civil War pension application papers. After the war, James married, became a carpenter, and had six children. He died at the age of 57 after a fall from some scaffolding. A coworker had called a warning that the scaffold was not secure, but he did not hear. His widow then applied for a Civil War pension.
<h6><img loading="lazy" decoding="async" class="alignright wp-image-25696 size-medium" src="https://blog-api.23andme.com/wp-content/uploads/2012/04/Trait-Chromosome-Diagram-293x300.jpg" alt="" width="293" height="300" srcset="https://blogcms.23andme.com/wp-content/uploads/2012/04/Trait-Chromosome-Diagram-293x300.jpg 293w, https://blogcms.23andme.com/wp-content/uploads/2012/04/Trait-Chromosome-Diagram.jpg 699w" sizes="auto, (max-width: 293px) 100vw, 293px" />Disability</h6>
There was some dispute about whether his hearing loss was a pre-existing condition, or whether it was related to his service, during which he had contracted the measles, a known cause of sudden deafness. He wrote in his own disability pension application:
“I was out of my head, and when I came to my senses the comrades of my company were taking care of me in the camp, and I was totally deaf, and have been severely deaf in both ears ever since.”
He was discharged, and his commanding officer wrote:
“This man was slightly deaf at the time of his enlistment. About the middle of October he was attacked with the measles and since his recovery he has been unable to hear even the loudest command.”
James would have been 18 at the time he enlisted, so if the hearing loss was noticeable at that age, he probably had both a hereditary and environmental explanation for his deafness. Some of his children were also known to be hard of hearing at a young age, but none of his living descendants still carry the trait (nor do any descendants of George).
<h6>What about the Genetics?</h6>
Those were some of the examples of the hearing impairment that we were able to trace through paper records, but what about the genetics? Could we trace the hearing impairment trait through DNA?
The Family Inheritance: Advanced tool at 23andMe is an easy way to visualize the chromosomal regions shared by different relatives. The figure shows four of the people I tested. They share the hearing loss, come from different lines of descent, and are the most distantly related possible. (Closer cousins share so many segments that the target wouldn’t stand out.) The answer to my initial question is a resounding yes! Other extended families may be able to follow this model of collecting cousins, which I have also described in a column for the <a href="http://www.jogg.info/52/files/SatiableCuriosity.pdf">Journal of Genetic Genealogy</a>.
James Lupski has proposed the term “clan genomics” for this type of endeavor.
Now what? The sense of hearing is complex, with numerous genes affecting structures and functions. To date, 122 different loci (that is, general locations) have been <a href="https://www.ncbi.nlm.nih.gov/pubmed/22016077">associated with hearing loss</a>. The actual gene has been identified for only half of those. None of the locations overlap the section implicated in our family, so we are exploring virgin territory. We’ve reduced the possibilities from 3 billion bases and 20-some thousand genes to a mere 15,000,000 bases and 278 genes (many with unknown functions), but there’s still a ways to go.
It’s highly unlikely that any of the SNPs in our genotype data from 23andMe are actually responsible, since the chip design focuses on relatively common variants. Thus I am participating in the exome pilot project at 23andMe, which will completely sequence the coding regions of all genes and (if we’re lucky) may identify a novel mutation. There may be no suspicious variants, or there may be a superabundance of potential candidates, but that’s part of the adventure.
In the meantime, I am always on the lookout for even more distant cousins who might harbor the same mutation. Circumstantial evidence makes John Riley the more likely ancestor, but he is a brick wall in my genealogy.
If the mutation originated with him, we might be the only people in the world to shed light on yet another gene important for the sense of hearing. If he inherited it from an ancestor, there might be other lines of descent out there who share some DNA with us in that part of chromosome 15. Either outcome would be intriguing.
To be continued…
23andMe’s services are not a substitute for professional medical or diagnostic advice.  Always consult your physician for medical or diagnostic advice.
Ann Turner received her undergraduate degree in biology in 1964 and her M.D. from Stanford University in 1970. Her interest in genealogy began in midlife, when she read a family memoir about her father’s ancestors coming to America in 1635 on the ship Abigail. She began thumbing through the passenger manifest, where she recognized another familiar name–one of her mother’s ancestors. One family had headed for Connecticut and another for Vermont. Their descendants–her mother and father–met and married 300 years later in Iowa.
She founded the GENEALOGY-DNA mailing list at RootsWeb in the year 2000, the same week she received results from the first commercially available mtDNA test at Oxford Ancestors. She is the co-author (with Megan Smolenyak) of Trace Your Roots with DNA: Using Genetic Tests to Explore Your Family Tree and writes a regular column called ‘Satiable Curiosity for the Journal of Genetic Genealogy. She has consulted with Sorenson Molecular Genealogy Foundation and 23andMe.

Ann Turner

Tracking Down a Trait

<img loading="lazy" decoding="async" src="https://blog-api.23andme.com/wp-content/uploads/2012/04/200901_omag_cover_220.jpg" alt="" class="aligncenter size-large wp-image-12132" width="1" height="1" srcset="https://blogcms.23andme.com/wp-content/uploads/2012/04/200901_omag_cover_220.jpg 220w, https://blogcms.23andme.com/wp-content/uploads/2012/04/200901_omag_cover_220-150x150.jpg 150w" sizes="auto, (max-width: 1px) 100vw, 1px" />What do media mogul Oprah Winfrey, actress Mary-Louise Parker, and Olympic runner Carl Lewis have in common?<img loading="lazy" decoding="async" src="https://blog-api.23andme.com/wp-content/uploads/2012/04/200901_omag_cover_220.jpg" alt="" class="alignright size-large wp-image-12132" width="1" height="1" srcset="https://blogcms.23andme.com/wp-content/uploads/2012/04/200901_omag_cover_220.jpg 220w, https://blogcms.23andme.com/wp-content/uploads/2012/04/200901_omag_cover_220-150x150.jpg 150w" sizes="auto, (max-width: 1px) 100vw, 1px" />
Aside from their more than 15 minutes of fame, all three have been diagnosed with hypothyroidism, a condition where the body does not make enough thyroid hormone. This, in turn, can lead to fatigue, depression, weight gain, and joint pain, among other symptoms. Hypothyroidism affects about 5% of the general population, mostly women over the age of 50, making it the most common thyroid disorder.
Hypothyroidism can result from an autoimmune disease such as Hashimoto’s thyroiditis, radiation therapy, or from treatment for hyperthyroidism (overactive thyroid). Genetics are especially likely to play a role in cases with no obvious underlying environmental cause. Despite its prevalence and “celebrity” status, however, the genetic factors influencing hypothyroidism are still mostly unknown.
In 2011, the <a href="https://www.ncbi.nlm.nih.gov/pubmed/21981779">first genome-wide association study of hypothyroidism</a> was published. A year later, 23andMe has published the second, and now largest, <a href="http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0034442">study of genetic factors</a> for the condition (<a href="https://www.23andme.com/about/press/hypothyroidism/">read more in our press release</a>). 
By comparing DNA and survey information from more than 3,700 people with hypothyroidism and about 35,500 people without the condition (all of European descent), we replicated previously observed genetic associations and discovered several additional genetic variants associated with hypothyroidism.
Two of these variants are near genes that have already been linked to thyroid disease. The C version of rs925489 near the FOXE1 gene (equivalent to the A version of rs7850258) is associated with slightly lower odds of hypothyroidism and the A version of rs2476601 near the PTPN22 gene is associated with higher odds of the disorder.
The PTPN22 variant is actually well-established as a risk factor for multiple autoimmune diseases.
A third association is with rs3184504 in the gene SH2B3, which has not been linked to thyroid disease previously but, like PTPN22, is associated with a number of autoimmune conditions. The C version of this SNP is associated with slightly lower odds of hypothyroidism. Similarly, another SNP associated with hypothyroidism in our study, rs2517532, is located in a region of the genome that is important for immune system function.
Our findings indicate that there is a significant autoimmune component to hypothyroidism, in addition to influences from genes directly related to thyroid function and hormone levels. Studies have shown that different autoimmune conditions cluster together, suggesting possible shared biology.
The association we report between SH2B3 and hypothyroidism is similar to the associations previously reported between this gene and psoriasis, type 1 diabetes, and rheumatoid arthritis, but different from the association between this gene and multiple sclerosis and celiac disease. The placement of hypothyroidism along the spectrum of autoimmune disease may help define future research into causes and treatments for this common disorder.

New genetic variants found to influence risk of hypothyroidism

<img loading="lazy" decoding="async" class="alignright size-medium wp-image-3837" title="DNA code analysis" src="https://blog-api.23andme.com/wp-content/uploads/2009/06/atcg-300x199.jpg" alt="" width="300" height="199" srcset="https://blogcms.23andme.com/wp-content/uploads/2009/06/atcg-300x199.jpg 300w, https://blogcms.23andme.com/wp-content/uploads/2009/06/atcg.jpg 425w" sizes="auto, (max-width: 300px) 100vw, 300px" />
The term “sarcoma” encompasses over a hundred forms of rare cancers, and the cause behind many of these forms is unknown.
<h6>More on Ewing Sarcoma</h6>
Ewing sarcoma, however, is one sarcoma for which the biology is relatively well understood.
This form is caused by a gene fusion &#8212; a DNA rearrangement resulting in two genes being fused together.  In the case of Ewing sarcoma, the fused genes are EWSR1 on chromosome 22 and typically FLI1 on chromosome 11. Although not much is known about risk factors for Ewing sarcoma, a <a href="https://blog.23andme.com/articles/ewing-sarcoma" target="_" rel="noopener">recent study</a> identified genetic variants associated with higher risk for the condition.
Now, a team of French researchers has uncovered the underlying cause of a new type of sarcoma: a different gene fusion.
<h6>New Research Findings</h6>
In this new study published in <a href="https://www.nature.com/ng/journal/v44/n4/full/ng.1107.html">Nature Genetics</a>, the team led by Olivier Delattre and GaÃ«lle Pierron studied tumors similar to Ewing sarcoma but lacking the EWSR1-FLI1 gene fusion, focusing primarily on bone sarcomas affecting adolescents and young adults. Altogether the researchers examined almost six hundred tumor samples and discovered that twenty-four of these tumors had identical genetic rearrangements &#8212; but a different one than that associated with Ewing sarcoma. This newly-discovered subtype of sarcoma results from a gene fusion between the BCOR and CCNB3 genes, both of which are located on the X chromosome.
<div style="border: 1px solid #000; padding: 10px; font-style: italic; margin-bottom: 15px; width: 200px; float: right; margin-left: 15px;"><img loading="lazy" decoding="async" class="alignleft size-full wp-image-12163" style="float: left; margin-right: 15px;" title="small_23andMe_logo" src="https://blog-api.23andme.com/wp-content/uploads/2012/04/JRBgdIBXKIeVIdETJrxYIw_ttam_logo.jpg" alt="" width="24" height="40" />You can help! If you&#8217;ve been diagnosed with any type of sarcoma, <a href="https://www.23andme.com/sarcoma">join 23andMe&#8217;s Sarcoma Research Community today</a>. Even if you don&#8217;t have sarcoma, you can still contribute to research by <a href="https://www.23andme.com/store">becoming a 23andMe customer</a> and answering surveys.</div>
The two genes involved in this new type of sarcoma both have important biological roles. The BCOR gene encodes a protein that regulates the activity of genes (specifically, genes within a type of stem cell found in bone marrow). Mutations in the BCOR gene can result in serious diseases, such as <a href="http://ghr.nlm.nih.gov/condition/oculofaciocardiodental-syndrome" target="_" rel="noopener">oculofaciocardiodental</a> and <a href="http://ghr.nlm.nih.gov/condition/lenz-microphthalmia-syndrome" target="_" rel="noopener">Lenz microphthalmia</a> syndromes. In addition, BCOR-CCNB3 is not the first documented gene fusion involving BCOR causing disease; when the BCOR gene fuses with the <a href="https://www.ncbi.nlm.nih.gov/pubmed/20807888">RARA</a> gene on chromosome 17, the result is another cancer that affects the blood and bone marrow.
<h6>CCNB3</h6>
The role of the second gene, CCNB3, is somewhat less obvious. This gene encodes a protein expressed only in the testis and is important for the formation of new sperm cells.
The researchers hypothesized that the production of this protein in cells outside of the testis was a key factor in this new type of sarcoma. Using additional experiments, they observed that increased levels of CCNB3 protein led to increased cell proliferation &#8212; a hallmark of cancer &#8212; and that out of nearly one thousand tumor samples, only tumors with the BCOR-CCNB3 gene fusion had high levels of the protein encoded by the CCNB3 gene.
Delattre and Pierron’s findings suggest that the BCOR-CCNB3 gene fusion is directly related to the development of this form of sarcoma. This type of sarcoma may also share other attributes with the better-understood Ewing sarcoma, which results from a different gene fusion. Such new knowledge will hopefully translate into better sarcoma diagnoses and, someday, better treatments.

Gene Fusions Point to a New Type of Sarcoma

As the series <a href="https://www.pbs.org/wnet/finding-your-roots/" target="_blank" rel="noopener noreferrer">Finding Your Roots with Henry Louis Gates, Jr.</a> continues its 10-week run on PBS, The Blog will feature posts from 23andMe’s Ancestry Ambassadors featuring their own stories about using DNA to dig into ancestry.
By Shannon Christmas
<img loading="lazy" decoding="async" class="alignright size-full wp-image-12107" title="shannon's gp" src="https://blog-api.23andme.com/wp-content/uploads/2012/04/shannons-gp.jpg" alt="" width="220" height="278" />
African American genealogy remains a challenging jigsaw puzzle where half of the pieces seem irrevocably lost. Many families scarred by chattel slavery buried their pasts to distance themselves and their progeny from the horrors of bondage.
<h2>A Fractured History</h2>
Now, advances in genetics and Internet technology have unearthed some of the long-buried pieces of our significantly fractured history.
Uncovering some of those missing pieces for my family required an open mind. One of my paternal great-grandmothers, Katie Lee Davis of Warren County, North Carolina, inherited a revisionist version of our family’s past.
In her correspondence with one of my cousins, Grandma Katie identified her ancestors, wrote lovingly of her paternal aunts, and recalled never having known a former slave among her relatives. Yet in 2010, 16 years after her death, revelations about Grandma Katie’s ancestors began to tell a different story. 

<img loading="lazy" decoding="async" class="alignright size-medium wp-image-12109" title="gravestone" src="https://blog-api.23andme.com/wp-content/uploads/2012/04/gravestone-300x225.jpg" alt="" width="300" height="225" srcset="https://blogcms.23andme.com/wp-content/uploads/2012/04/gravestone-300x225.jpg 300w, https://blogcms.23andme.com/wp-content/uploads/2012/04/gravestone.jpg 453w" sizes="auto, (max-width: 300px) 100vw, 300px" />
Marriage and death records from Warren County list Grandma Katie’s paternal grandparents as Henry and Lucinda Davis, an African-American couple about whom little else is known.
<h2>A Pedigree</h2>
However, in the summer of 2010, Ray, the husband of one of my father’s first cousins, emailed me a pedigree outline that omitted Henry’s name and replaced it with a Peter “White” Davis. The glaring conflict between the government documents I had examined and this new email raised questions.
Who was Peter “White” Davis? Was he really Grandma Katie’s grandfather?
The answers to those questions only heightened my curiosity. Ray reported that Peter “White” Davis, a slave owner formally named Peter Randolph Davis, allegedly sired many mulatto children with his slaves. According to one of Katie’s elderly distant relatives, Grandma Katie’s father, Richard D. Davis, was one of those mulatto children.
<img loading="lazy" decoding="async" class="alignright size-medium wp-image-12108" title="erasmuschristmas" src="https://blog-api.23andme.com/wp-content/uploads/2012/04/erasmuschristmas-222x300.jpg" alt="" width="222" height="300" srcset="https://blogcms.23andme.com/wp-content/uploads/2012/04/erasmuschristmas-222x300.jpg 222w, https://blogcms.23andme.com/wp-content/uploads/2012/04/erasmuschristmas.jpg 225w" sizes="auto, (max-width: 222px) 100vw, 222px" />
Tracing Peter Randolph Davis’ lineage yielded another discovery. Peter’s maternal great-grandparents included a couple I had encountered in previous research: Captain William Green and Mary Elizabeth Christmas. Captain Green and his wife, Mary, were indirect ancestors of my great-grandfather, Richard Christmas.
<h2>A Warren County Planter</h2>
Richard Christmas’s paternal grandfather, Lewis Yancey Christmas, a wealthy Warren County planter and attorney, took two slaves as common-law wives. The first union produced 12 children, including my great-great-grandfather, Erasmus Christmas.
If the Peter Randolph Davis story was accurate, then my great grandfather Richard Christmas and my great grandmother Katie Lee Davis were not only husband and wife for 60 years, but 4th cousins once removed.
The possibility of a consanguineous marriage, though initially unsettling, provided an opportunity to verify this new paternity claim using DNA testing. Web-based DNA analysis tools allow one to search an individual’s raw DNA data file from 23andMe for runs of homozygosity and DNA segments indicating one’s parents shared recent common ancestors.
<h2>Cousin Test</h2>
Since my grandfather, the son of Richard Christmas and Katie Lee Davis had tested with 23andMe, the truth sat just a few keystrokes away. GEDMatch.com’s “Cousin Test for Parents” identified nine runs of homozygosity among my grandfather’s 22 autosomal chromosomes, amounting to more than 55 centimorgans (cM) of DNA, an amount that suggests his parents were at least 4th cousins.
A similar tool created by mathematician David Pike (<a href="http://www.math.mun.ca/%7Edapike/FF23utils/roh.php">http://www.math.mun.ca/~dapike/FF23utils/roh.php</a>) replicated the results. Richard Christmas and Katie Lee Davis shared a bloodline, proving that Peter Randolph Davis was Katie’s paternal grandfather.
<img loading="lazy" decoding="async" class="alignright wp-image-12111 size-medium" title="shannondoc" src="http://35.88.189.111/wp-content/uploads/2012/04/shannondoc-218x300.jpg" alt="" width="218" height="300" srcset="https://blogcms.23andme.com/wp-content/uploads/2012/04/shannondoc-218x300.jpg 218w, https://blogcms.23andme.com/wp-content/uploads/2012/04/shannondoc.jpg 473w" sizes="auto, (max-width: 218px) 100vw, 218px" />
In early 2012, I obtained a slave inventory from an estate file for Dr. Stephen Davis (Peter Randolph Davis’ father); the family of Henry and Lucinda Davis appears among the slaves listed.
Like so many former slaves, the paternal relatives with whom my great-grandmother spent her earliest years clearly sought to conceal their dark history to embrace a brighter future. But DNA illuminated how that past proved prologue.
23andMe provides genetic testing services for informational purposes; your results may or may not help you find or identify relatives or family members.
When not updating pedigree charts or mapping his chromosomes, Shannon Christmas is the founder and Chief Market Advisor/Design Strategist of The Christmas Collective, a strategic real estate and land use consulting atelier.

Shannon Christmas

The Missing Pieces in an African American Family History

<img loading="lazy" decoding="async" class="alignright wp-image-4013 size-full" title="geneticresearch7" src="http://35.88.189.111/wp-content/uploads/2009/07/geneticresearch7.jpg" alt="" width="350" height="268" srcset="https://blogcms.23andme.com/wp-content/uploads/2009/07/geneticresearch7.jpg 350w, https://blogcms.23andme.com/wp-content/uploads/2009/07/geneticresearch7-300x230.jpg 300w" sizes="auto, (max-width: 350px) 100vw, 350px" />
Recently, Todd Sherer, CEO of The Michael J. Fox Foundation (MJFF), Brian Fiske, vice president of research programs at MJFF, and Emily Drabant, 23andMe’s research manager for its <a href="https://www.23andme.com/pd/" target="_blank" rel="noopener noreferrer">Parkinson’s community,</a> sat down and took stock of the recent advances in Parkinson’s research.
Their conversation centered around new understandings of the genetics of Parkinson’s disease that could form the building blocks for research over the next decade.
Learning more about the role genetics plays in Parkinson’s could provide life changing new treatments for people living with the disease. &nbsp;Much of the work to this end is currently focused on a particular mutation in the LRRK2 gene. About one in 10,000 people have this particular mutation – G2019S – which is associated with a 50 percent lifetime risk of Parkinson’s compared to about one percent in the general population. While this association is well established, the role the mutation plays in the development of the disease is less clear. Researchers, however, have made some important breakthroughs offering insight into the possible role that LRRK2 plays in developing the disease, as well as how genetics may interact with environmental factors to cause Parkinson’s.
<h6>LRRK2 and Neuroinflammation</h6>
Fiske said new data suggests the body’s immune system, particularly the<a href="https://www.ncbi.nlm.nih.gov/pubmed/21552986"> inflammatory response in the brain</a>, may play a key role in the development of Parkinson’s. Inflammation is the body’s response to injury, but the response, particularly an exaggerated immune response, could lead to harmful neuroinflammation. It appears that one component of Parkinson’s is this harmful neuroinflammatory response. 
Researchers, supported by MJFF, are studying whether the LRRK2 mutation leads to a more exaggerated inflammatory response. &nbsp;To date, the data are looking very interesting in this direction.
<img loading="lazy" decoding="async" class="alignright wp-image-12055 size-medium" title="DSC_5239_Todd Sherer, PhD" src="http://35.88.189.111/wp-content/uploads/2012/04/DSC_5239_Todd-Sherer-PhD-201x300.jpg" alt="" width="201" height="300" srcset="https://blogcms.23andme.com/wp-content/uploads/2012/04/DSC_5239_Todd-Sherer-PhD-201x300.jpg 201w, https://blogcms.23andme.com/wp-content/uploads/2012/04/DSC_5239_Todd-Sherer-PhD-768x1147.jpg 768w, https://blogcms.23andme.com/wp-content/uploads/2012/04/DSC_5239_Todd-Sherer-PhD-589x880.jpg 589w, https://blogcms.23andme.com/wp-content/uploads/2012/04/DSC_5239_Todd-Sherer-PhD-790x1180.jpg 790w, https://blogcms.23andme.com/wp-content/uploads/2012/04/DSC_5239_Todd-Sherer-PhD-686x1024.jpg 686w, https://blogcms.23andme.com/wp-content/uploads/2012/04/DSC_5239_Todd-Sherer-PhD-scaled.jpg 1715w" sizes="auto, (max-width: 201px) 100vw, 201px" />Todd Sherer, PhD
Sherer said that one high level theory is that if this connection is real this could explain why not everyone with the LRRK2 mutation develops Parkinson’s.
“To activate the immune system response you need some kind of trigger,” he said. “It may take a trigger to interact with the genetics, but no one has tested for this yet.”
<h6>LRRK2 And Cellular Pathways</h6>
Just as in everyday life we accumulate clutter and waste that eventually has to be thrown out, inside our bodies our daily functions produces trash of sorts that has to be cleared out. Our cells actually have a sort of self-cleaning mechanism called “autophagy” that clears out junk protein and other cellular debris.
Parkinson’s researchers have found that this process is somehow broken in patients with the LRRK2 mutation. Studies are focused on whether decreased autophagy may make cells in the brain more susceptible to Parkinson’s-related cell death. Researchers want to know if this is a cause for the disease or simply an effect from it, said Fiske.
<img loading="lazy" decoding="async" class="alignright wp-image-12056 size-medium" title="Brianfiske" src="http://35.88.189.111/wp-content/uploads/2012/04/Brianfiske-300x200.jpg" alt="" width="300" height="200" srcset="https://blogcms.23andme.com/wp-content/uploads/2012/04/Brianfiske-300x200.jpg 300w, https://blogcms.23andme.com/wp-content/uploads/2012/04/Brianfiske-880x586.jpg 880w, https://blogcms.23andme.com/wp-content/uploads/2012/04/Brianfiske-768x511.jpg 768w, https://blogcms.23andme.com/wp-content/uploads/2012/04/Brianfiske-1024x681.jpg 1024w, https://blogcms.23andme.com/wp-content/uploads/2012/04/Brianfiske-1180x785.jpg 1180w" sizes="auto, (max-width: 300px) 100vw, 300px" />Brian Fiske, PhD
<h6>LRRK2 Clinical Observations</h6>
Researchers are comparing individuals who have the LRRK2 mutation and Parkinson’s with people who have developed the disease but don’t have the LRRK2 mutation. These patients who have the disease but don’t have the mutation are also known as “idiopathic” Parkinson’s patients. Researchers found that while the disease in these two types patients appears to be very similar, in some cases the LRRK2 patients have somewhat milder symptoms. For instance, the loss of smell is less pronounced in LRRK2 patients.
According to Fiske work comparing these patients has also highlighted some other intriguing links that researchers would like to explore.. For example, there is an apparent link between LRRK2 and an increased risk for non-skin cancers. This may have to do with a shared genetic background among people of similar ancestry, for instance, instead of some other causal link, but The Michael J. Fox Foundation’s LRRK2 Cohort Consortium is looking into this connection.
<h6>Other Genetic Factors for Parkinson’s</h6>
When exploring the genetics underlying the disease, researchers are still trying to understand why the LRRK2 mutation sometimes doesn’t lead to development of the disease. Scientists also want to know why the age at which a person develops Parkinson’s is so variable, said Sherer. What is clear is that there are other genetic and environmental factors involved.
<img loading="lazy" decoding="async" class="alignright size-medium wp-image-12100" title="emily" src="https://blog-api.23andme.com/wp-content/uploads/2012/04/emily-240x300.jpg" alt="" width="240" height="300">Emily Drabant, PhD
And while there is a lot of focus on the LRRK2 mutation, other genetic factors are also involved. Last year 23andMe found<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002141"> two new genetic associations</a> with the disease and more recently found a genetic variant,<a href="https://www.23andme.com/about/press/sgk1/"> SGK1,</a> that is potentially protective against the disease. Other genetic mutations associated with the disease include one protein primarily found in brain tissue called alpha-synuclein, which is encoded by the SNCA gene. Researchers have found that alpha-synuclein accumulates and clumps together in the brain of Parkinson’s patients. There currently is a clinical trial for a drug that specifically targets these clumps of alpha-synuclein as a way to treat Parkinson’s patients.
There are other genetic variants that are also being looked at, and there is a much broader effort to do a sort of “mega” meta-analysis that would develop a master list of common genetic variants associated with the disease. It’s believed that together these genetic variants account for about a quarter of all Parkinson’s cases, but most of those genetic associations have yet to be discovered. 23andMe and MJFF &nbsp;are part of this large-scale effort. Some of this work may be helped as the cost of exome sequencing and full genome sequencing continues to drop. Most recently an association with a variant in the VPS35 gene was found through exome sequencing. 
“It’s one of the first PD genes found (through exome sequencing) so it represents a technological turning point away from the classic (genome-wide association study) approaches in the past,” said Fiske. “It seems to play roles in pathways involved in transport of proteins around the cell, but we have little understanding yet of how it might lead to Parkinson’s.”
<h6>Parkinson’s Indicators</h6>
Another thrust of the research is into biomarkers that can be used to track the progression of Parkinson’s and may help in early intervention. It could be that looking at alpha-synuclein or another protein called DJ-1 may offer a good way to track the disease. In the case of alpha-synuclein, it might be that detecting clumps of the protein could offer a good measure. There is also the possibility of piggybacking on a technique developed for brain imaging of Alzheimer’s disease. That method, looking at the beta-amyloid protein, could be copied in some way with Parkinson’s patients. 
Researchers are now able to use a brain scan, called the DATSCAN, to measure dopamine in the brain. But while the scan is good for detecting deficits in people in early stages of the disease, those deficits don’t change significantly after a patient has full-blown Parkinson’s, said Fiske. New imaging technologies could be used not just to diagnose the disease and its progression, but also to test the effectiveness of drug treatment.
Finally, while there is a lot of attention focused on treatment, there is also work being done to try to detect Parkinson’s earlier and earlier. Researchers already know that people in Parkinson’s earliest, or “pre-motor” phase, have distinct symptoms, such as loss of smell, sleep problems and constipation. In combination, those symptoms can be a good predictors of Parkinson’s. By identifying those with high risk of developing the disease, it may be easier to target them with new drugs or other therapies to prevent them from ever developing Parkinson’s.
<h6>Conclusion</h6>
New understandings of the genetics of PD offers much to be hopeful about. Parkinson’s is an extremely complex disease, but researchers are finding more and more pieces in our effort to complete our understanding of this sometimes puzzling disease. We are lucky to have so many resources to help us do that. This update really only scratches the surface of the work being done to find treatment and a cure for Parkinson’s. We hope to follow up with another update on the promising Parkinson’s research later this year.

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