Health at 23andMe: L’Chaim, Sheridan!

Editor’s note: Pending an FDA decision, 23andMe no longer offers new customers access to health reports referred to in this post. Customers who purchased prior to November 22, 2013 will still be able to see their health reports, but those who purchased after that time will not. Those customers will have access to ancestry information as well as access to their uninterpreted raw data.

If you saw adoptee Sheridan* on the street, you might wonder — as she does — about her ancestral origins. You could guess a few things, but would you have guessed she has Jewish ancestry? It turns out a small percentage of her ancestry is Ashkenazi, a fact she learned recently from her 23andMe Ancestry Composition.

At the time, she didn’t think much about it. She and her friend Brian were busy comparing their ancestries to those of their friends. But it seemed to Sheridan that Ashkenazi Jewish ancestry got mentioned a lot in discussions about genetics. She decided to ask Brian, who knows a lot about genetics, about this.

He thought for a second. “Well, traditionally Ashkenazi Jews have married within their community – over time this has led to a pretty genetically interesting group.”

“What do you mean?” she asked.

“For one thing,” he said, “because any two Ashkenazi Jews are likely to share recent common ancestors, they are more likely to share long identical stretches of DNA than are people from most other populations. This can be tricky for predicting genetic relationships.”

“Ok,” said Sheridan. “So what might that mean for me if I have a little bit of Ashkenazi ancestry?”

“Having just a little probably doesn’t make a big difference for your genetic relative predictions…” Brian stopped to think. “But there are also potentially some health implications. Have you looked at your health results for inherited conditions recently?”

“Hmm, I did when I first got my results back, but not recently,” she said.

“23andMe’s added some new health reports in that category lately so maybe we should check it out again,” suggested Brian. “It could be valuable for you to know if you have any genetic variations that could affect the health of your kids.”

As an adoptee, Sheridan saw a family medical history as something of a pipe dream, so this got her interested. Her DNA could potentially fill in some of the missing picture.

Sheridan logged into her account and pulled up her results for the inherited conditions covered by 23andMe. At the top of the list two conditions were highlighted as having a “Variant Present.” This meant that out of the genetic mutations covered in each report (usually the most common mutations), 23andMe had detected at least one of them in Sheridan’s DNA.

“Whoa.” Sheridan squinted at the screen. “Beta thalassemia… and familial… hyper…insulinism.” The names seemed like a mishmash of familiar and foreign words in strange combinations.

“Yeah, disease names can be a mouthful” said Brian. “But let’s see what these are about.”

They went to the Beta Thalassemia report first. Beta thalassemia is a genetic blood disorder that can cause anemia.

“This report was added in the summer of 2012,” Brian recalled, “which is great because it’s actually fairly common and it can affect people from all ancestral backgrounds.”

The report told Sheridan that she had one genetic mutation in the HBB gene associated with beta thalassemia and could pass it on to her children. People with one such mutation are said to have “beta thalassemia minor.”

“What does that mean?” Sheridan wondered. “Should I be worried?”

“Not necessarily,” said Brian. “I think that’s just what they call carriers for beta thalassemia, or people with one mutation. This condition is considered ‘recessive,’ meaning you need to have two mutations in order to have the disease, but in this case it may be possible for people with just one mutation to have mild symptoms because of how the mutation works. That’s still pretty unlikely, but it might not hurt to let your doctor know you have this mutation in case you ever do have problems related to it. And obviously it’s good to know in case you have children since they could inherit this mutation from you.”

“Ok. I’ll bring it up at my next checkup. So you said this is relatively common?”

“Yeah, at least in certain populations. Let’s see…” he scanned the report. “It says 1.5 percent of people are carriers for this condition, meaning they have one mutation like you. Mostly people from the Mediterranean, Middle East, India, Asia, and Africa — which is where I’m guessing your mutation came from.”

“How could we know?” she asked.

“Well, we might not know for sure, but we can see which exact mutation you have and see what the research says.” Brian clicked to the “Technical Report” and they saw that Sheridan had the mutation known as c.-79A>G (also identified as ). After some quick sleuthing they found that the mutation is considered to be the most common mutation in people with African ancestry.

They then turned their attention to Sheridan’s other result, Familial Hyperinsulinism. This particular report is specific to mutations in a gene called ABCC8. Mutations in this gene cause high insulin levels (hyperinsulinism) and people with the condition have dangerously low blood sugar levels as a result. The condition can be managed well if caught early.

The “Founder Effect” on Health

Certain populations of people living today can all trace their roots back to a small group of “founders.” Due to geographic and religious isolation, they married only within their community. Through the generations, genetic mutations that were present in just one or a few of the founders became more common in this population, resulting in the higher frequencies of inherited disease seen today in people from these groups.

For example, the mutations causing Tay-Sachs disease, Gaucher disease, and Canavan disease are more common in people with Ashkenazi Jewish ancestry; mutations causing sickle cell anemia and beta thalassemia are more common in people with African ancestry, and mutations causing Leigh syndrome are more common in people with French-Canadian ancestry.

Again, Sheridan was reported as having one mutation, so she wasn’t expected to have the condition, but she could pass the mutation on to her children. Looking at the Technical Report for this condition, they saw that her specific mutation was called 3989-9G>A and that this mutation accounts for about 70 percent of the mutations found in people with Ashkenazi Jewish ancestry. In fact, one out of 60 Ashkenazi Jewish individuals has this mutation.

“Aha! I knew it!” said Brian.

Sheridan was amazed. “Who would have thought just 2.3 percent of Ashkenazi Jewish ancestry could matter so much?” But apparently where that ancestry lay in her genome mattered, too. It just so happened that her Ashkenazi Jewish ancestor had this mutation linked to familial hyperinsulinism, and Sheridan had ended up with that specific piece generations later.

“And you know what’s the crazy part?” Brian continued. “No one would have expected you to have a mutation for that disease, since you don’t look like who they normally associate with having one.”

It was official. Sheridan’s DNA had not only given her insights into her ancestry, it had also shown her hidden aspects of her health. And that had the potential to benefit not just Sheridan, but also her children and grandchildren.

*Sheridan is a fictional character.