Have a Stutter? It Could Be Inherited

For a long time, scientists have suspected that stuttering — a common speech condition that affects an estimated 1 in every 100 people — could be heritable. Despite how common it is, it's still a remarkably understudied condition. Geneticists Piper Below https://medicine.vumc.org/department-directory/Jennifer-Below and Dillon Pruett https://fda.fsu.edu/nfd/dillon-pruett were determined to fix that. With the help of 23andMe data, they recently identified 57 genetic regions linked to stuttering in the human genome. Their findings represent a new breakthrough in how researchers think about speech conditions, genetics and the conditions that are linked to them. They're what some are calling a "quantum leap" in the field. Interested in more human biology and genetics episodes? Email us your question at [email protected] mailto:[email protected]. Listen to every episode of Short Wave sponsor-free and support our work at NPR by signing up for Short Wave+ at plus.npr.org/shortwave http://plus.npr.org/shortwave. See pcm.adswizz.com https://pcm.adswizz.com for information about our collection and use of personal data for sponsorship and to manage your podcast sponsorship preferences. NPR Privacy Policy https://www.npr.org/about-npr/179878450/privacy-policy

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• 0:00Emily Kwong?

  This message comes from NPR sponsor Viori with the Halo Essential Wide-Like Pant. Receive 20% off your first purchase at viori.com/NPR on any US orders over $75 and free returns. Exclusions apply. Visit the website for full terms and conditions. You're listening to Short Wave from NPR. Hey, Shortwavers. Emily Kwong here. And today, we're going to meet Dylan Pruitt, a genetics researcher at Florida State University in the School of Communication Sciences and Disorders. And the particular condition Dylan studies, it's been with him most of his life.

• 0:37Speaker 01

  I started stuttering around age three, throughout elementary school, was in speech therapy.

• 0:44Emily Kwong?

  An estimated one in 100 people have a stutter, according to the National Institute of Health. That's 3 million Americans. But it is still an understudied condition. Dylan told us that even in college, there wasn't a lot of robust scientific knowledge about stuttering, what causes it, and why some people who start stuttering in childhood eventually stop, while others do not.

• 1:07Speaker 01

  I had kind of heard like, oh, there were some new studies that were looking at genetics of stuttering, and reached out to a professor and asked him questions. And he was like, you know, honestly, this is a very new area. I don't know a lot about it, but it's an area that needs a lot more research.

• 1:27Emily Kwong?

  So Dylan decided this was it. This was the research he wanted to pursue. And while it was frustrating that there were very few answers.

• 1:36Speaker 01

  It was, in another way, kind of inspiring, realizing that I could take action and pursue this field of study and really contribute to the field.

• 1:48Emily Kwong?

  Alongside geneticist Piper Bealow and her team of researchers at Vanderbilt University, Dylan recently released a paper that is making waves within the field. Published in the journal Nature Genetics, the study identifies 57 genetic regions linked to stuttering and what other conditions stuttering may be related to. Today on the show, a breakthrough in stuttering research. How a simple 23andMe survey led to new genetic insights and directly challenges misconceptions about what causes stuttering in the first place. I'm Emily Kwong, and you're listening to Short Wave, the science podcast from NPR.

• 2:28Speaker 02

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• 2:32Emily Kwong?

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• 2:47Speaker 02

  This message comes from BetterHelp. Your brain has limited storage, so why is it still holding on to that embarrassing moment from years ago? BetterHelp is an online therapy platform that gives you space to talk about what's taking up too much of yours. BetterHelp is now in-network with more than 125 health plans, with mini co-pays as low as $15 for eligible members. And if you don't have eligible insurance, you can still get 20% off your first month. Visit betterhelp.com/NPR. Cost and coverage may vary. Discount cannot be combined with insurance.

• 3:21Emily Kwong?

  This message comes from Capella University. That spark you feel? That's your drive for more. Capella University's FlexPath learning format lets you earn your degree at your pace without putting life on pause. Learn more at capella.edu. OK, so to learn about the genetics of stuttering, I called up both Piper Bielow and Dylan Pruitt, who worked on this study. And I started by asking them, OK, you guys, what's the main research question you were hoping to answer?

• 3:48Speaker 03

  Yeah, there has been an awareness for a very long time that stuttering is a trait that is very enriched in families. Meaning that if you are a person who stutters, you have a much higher likelihood of having a second or third individual in your family who also stutters than you would expect by chance. But another really common explanation is that there's some environmental exposure that is common to everyone within a family or within a household. And so in this case, we were really interested in tackling this question of whether or not we see this clustering of stuttering within families as a result of genetic factors.

• 4:32Emily Kwong?

  Yeah.

• 4:33Speaker 03

  And so we were very excited to be able to try to pinpoint the specific genes and variants that were contributing.

• 4:41Emily Kwong?

  And to pursue this question, you needed a massive data set that connected stuttering to genetics. You can't just, like, find one out there with a search on the internet. Where did you get one?

• 4:52Speaker 03

  Yeah, that's a great question. So we have been working on this question for, gosh, 15, 20 years now. But after years and years and years, had only amassed about 1,500 or 2,000 people who stuttered.

• 5:08Emily Kwong?

  Okay.

• 5:08Speaker 03

  It became apparent to me that in order to give this research the same sort of power for discovery as what we see being published every day for traits like diabetes, or Alzheimer's disease, or obesity, we would need to find a biobank that we could tap into that could provide both data on stuttering and genetic information at a really large scale. And it was so exciting when a colleague of mine sent me a message. She was at a research conference. She saw a poster being presented that had a snapshot of some questions from the 23andMe survey for people that consent to research.

• 5:51Emily Kwong?

  This being the genetic ancestry testing service for people to figure out, like, where their family's from, secret cousins they never knew they had, kind of stuff.

• 6:00Speaker 03

  Exactly, exactly. So this direct-to-consumer genetic testing company, 23andMe, had a question on their survey that was, you know, do you ever have, you know, have you ever had a stutter or a stammer?

• 6:12Emily Kwong?

  It's pretty incredible. You really got the granddaddy of biobanks when it comes to stuttering research. No, really. And I understand that this study, what also makes it unique, in addition to having access to 1.1 million users via 23andMe who reported whether they had ever had a stutter or had not, what also makes your study unique is that it was a genome-wide association study. Dylan, what does that mean, a genome-wide association study?

• 6:48Speaker 01

  Approach that is looking at areas of the genome that are kind of known to vary, and then analyzing them to see if they are associated with a trait. You know, when we look at everybody that has this trait and everybody that does not have this trait, what are the handful of variants that are associated with that trait?

• 7:11Emily Kwong?

  Of like genetic variants?

• 7:12Speaker 01

  Correct, correct.

• 7:14Emily Kwong?

  So you're saying that through this process, you'd be able to see every single gene that's potentially linked to stuttering?

• 7:18Speaker 03

  Exactly right, exactly right. And that led us to hypothesize, maybe this is a trait that is more like the diabetes, obesity, height, kinds of traits. And the genetic architectures of those have all been shown to be highly polymorphic, meaning there's a large number of variants from all across the genome that all, you know, some might increase your risk a little bit, others might decrease your risk a little bit. You can almost think of it like you're putting sand on either side of a teeter totter, and eventually if one side becomes heavy enough, then it flips and, you know, you have a higher risk for this trait.

• 7:56Emily Kwong?

  Yeah.

• 7:57Speaker 03

  And indeed, what we found was completely consistent with that hypothesis. We ended up revealing nearly 60 genomic regions across the whole human genome that were, you know, contributing small bits of additional risk of developing a stutter.

• 8:13Emily Kwong?

  That must have been so gratifying. Were any genes real standouts for you as like playing an outsized role in contributing to the emergence of stuttering?

• 8:23Speaker 03

  Yes, absolutely. The day we got the summary results released by 23andMe and transferred over to us, and I opened the file to look at the results, I actually had to sit down because the number one gene that emerged from our study was this gene VRK2. And the reason why that made me actually like took my breath away was because

• 8:49Emily Kwong?

  VRK2?

• 8:50Speaker 03

  That gene had just come out a few months prior as the number one hit.

• 8:57Speaker 03

  In a very large analysis of rhythm ability, people's ability to clap to a beat. And so this was the first time anybody actually had found a shared genetic underpinning underlying both developmental stuttering and this sort of rhythmicity, rhythm and musicality phenotype or trait.

• 9:20Speaker 01

  Yeah, I mean, I think it was really intriguing. And not only was it found as a top hit in the musical beat synchronization, but it was also the top hit in a couple of other independent studies that were looking at language as well. And so knowing that speech and language is so intricately tied and knowing that essentially the primary deficit in stuttering is really the timing of speech, it really blew me away. I think this gives us a really unique direction to explore.

• 10:02Emily Kwong?

  I love this discovery because it suggests one of the potential genetic causes is a rhythmic difference, like just the musicality of someone's speech is different. Not bad, just different.

• 10:17Speaker 01

  Yeah, yeah. And I think that when you are caught in a moment of stuttering, it does feel like the inability to move forward or to push past a sound. And so having these external timing mechanisms that can increase fluency, that might be generating some external cue that is lacking internally to a degree or is misaligned to a degree.

• 10:46Emily Kwong?

  Okay. Are there any other notable genetic tidbits that emerged from?

• 10:55Emily Kwong?

  This study, any other associations beyond misalignment around rhythm?

• 11:01Speaker 01

  Yeah, we observed positive correlation in males and females with depression. We also found correlations with autism and negative correlations with the beat synchronization. And so those are all features that we sometimes see associated with stuttering clinically. And so the genetic correlation is showing that there might be a genetic basis for those clinical associations that we see.

• 11:35Emily Kwong?

  Do you think, do you now think there might be different subtypes of stuttering?

• 11:39Speaker 03

  Oh, so there are different subtypes of stuttering. And this actually leads me back to what I was alluding to before about these really fascinating sex differences. So when kids turn, you know, about three, the onset of stuttering is approximately equal between girls and boys. But what's really interesting is that 80% of kids who stutter go on to recover, whether through therapy or spontaneous recovery. But most of those that recover are girls. And if you don't recover as a child, you are very likely to stutter for life.

• 12:20Speaker 03

  And this is what we call a persistent stutter versus a recovered stutter, which typically happens in fairly early childhood.

• 12:28Emily Kwong?

  So are you saying the subtypes fall along biological sex lines?

• 12:32Speaker 03

  Yeah, yeah, they do. And we don't understand why, you know, what is different about girls and boys, especially as they go through this transition around age, you know, seven or eight, that explains this difference.

• 12:46Emily Kwong?

  Dylan, going back to you, why does this research matter so much? And how can it support people who stutter?

• 12:55Speaker 01

  I think that for decades, we've been trying to look at the stuttering puzzle by looking at the pieces in isolation. And so that's the behavioral patterns, the neural circuits for speech, the role of language. And each of these have given us valuable clues, but they haven't been able to connect the dots. And so one of my hopes is that genetics could offer a mechanistic framework, or a way to see how these kind of separate domains are all interconnected and shaped by the underlying biology.

• 13:34Emily Kwong?

  Yeah, that's so interesting. Well, I got to ask you this then, too. How do you hope this research then shapes treatment? Dylan, is this about finding a cure for stuttering?

• 13:44Speaker 01

  Yeah, I don't really see our research as being about finding a cure for stuttering. I view our work as really about de-mystifying it. I think that stuttering is a beautiful, and in my view, underappreciated example of neurodiversity. And so our work helps us understand the genetic script behind that diversity. I think that instead of a one-size-fits-all approach, perhaps we could move towards more personalized support strategies to tailor towards an individual's unique neurobiology. And this can be really powerful and maybe

• 14:28Speaker 01

  empowering for people who stutter and their families.

• 14:35Speaker 03

  Yeah, absolutely. I don't think of this as a discovery that is sort of closing the door on a chapter in stuttering. I feel like we just threw every door and window open. Right? This is us approaching a starting line, not a finish line.

• 14:54Emily Kwong?

  Dylan and Piper, thank you so much for talking to us.

• 14:59Speaker 01

  Thank you. It's really been a pleasure.

• 15:01Speaker 03

  Yeah, it's been really great to talk to you.

• 15:03Emily Kwong?

  This episode was produced by Hannah Chin and edited by our showrunner Rebecca Ramirez. Tyler Jones checked the facts. Kwesi Lee was the audio engineer. Special thanks to John Hamilton. Beth Donovan is our senior director, and Colin Campbell is our senior vice president of podcasting strategy. I'm Emily Kwong. Thank you for listening to Shorewave from NPR.

• 15:26Speaker 02

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