Dr. Alisa Lehman - Exploring the genetic roots of Misophonia with 23andMe.
Transcript
Adeel [0:01]: Welcome to the Misophonia Podcast. This is episode 16. My name is Theo Mott, and I have Misophonia. So, usually I talk to fellow Misophonia sufferers about their conditions, how they've dealt with it, their experiences since their early memories. Occasionally I bring on a special guest from the clinical or research worlds to add some perspective on what the heck might be going on with us, and what's the latest research out there. Well, in this episode, I'm really happy to bring a conversation with Dr. Elisa Lehman, a senior product scientist at 23andMe. 23andMe, as you might know, is a consumer genetic analysis company that does tests on your DNA and gives you various reports, including your likelihood to have various health conditions. One of the reports that got my attention, obviously, is the one that tells you how likely you are to have misophonia. Specifically, how likely you are to hate the sound of chewing. Over the past couple of years, I found a lot of people who did 23andMe had the same question. So I was really curious to talk to someone at 23andMe and hear more about the research behind this. I'm really grateful to Dr. Lehman and Christine and Will and the whole team over there. You can find out more about 23andMe at 23andMe.com. Now, we probably have some new listeners, and if you're new to the podcast, I just want to point out that I do a number of things during post-production to make the shows more misophonia-friendly or sensory-friendly. For example, you're hearing some white noise, actually lower frequency brown noise that I've added to the background. I'm not... actually recording this next to a waterfall, this is added to help mask out some minor mouth triggers from the people speaking on the shows, and also to help mask some sounds that might be around you as you're listening. Other speech-related sounds are carefully cut out of the audio altogether to try and leave clean and even audio tracks. Now, don't forget to check out the show notes. I've got the 23andMe Misophonia white paper and their blog posts over there. So definitely check those out. But without further ado, here's my conversation with 23andMe scientist, Dr. Elisa Lehman. So, yeah, welcome, Dr. Lehman, to the podcast.
Alisa [2:20]: Thank you for having me.
Adeel [2:21]: Yeah, so maybe I thought we can start with just a little bit of background, kind of at a high level. Like, what is 23andMe? I know it does a lot of things.
Alisa [2:31]: Sure. So 23andMe is a direct-to-consumer genetic service. So what that means is essentially you can go on to 23andMe.com and order a kit or go to some retail stores. And the kit gets sent to you, and it's a saliva collection sample, so you just spit in a tube, send that back to our lab, and that analyzes your DNA. And basically from then, you can log back onto the 23andMe website and get your own sort of private portal where you can see results on all kinds of different topics, everything from your ancestry to certain health conditions that you might be predisposed to.
Adeel [3:11]: Yeah, I know you guys have been, it seems like you guys have been adding more and more. I think I did the kit like more than 10 years ago. And every time I go in, there seems to be new stuff there. And what do you do in particular for At23B?
Alisa [3:22]: So I am one of the senior product scientists on the team. And what we do is we work mostly on the health side of the product, which includes our trait reports, our wellness reports, and our health predisposition reports. And what we do is we dig into the science and make sure that everything that we're telling customers is scientifically accurate. But we also then write the reports themselves. So we make sure that those reports are then consumer friendly and so people can actually understand the science that we've taken the time to dig into.
Adeel [3:52]: Gotcha. Okay. Yeah. And so I'm going to obviously have links to the blog post and the report in the, in the show notes, but yeah, maybe we can, we can talk about the report. So I guess it looks like a, like a, there's a lot of questions that you can voluntarily answer on in your 23andMe profile. What did this, so I guess this kind of started with a, with a survey. Can you talk about like what their survey in particular asked in particular for, for this report?
Alisa [4:21]: Sure, yeah, so one of the optional things that you can opt into if you choose to with 23andMe is you can opt in to participate in research. And typically that is a survey. So you can go again onto that secure portal, answer survey questions, and then what we do is we have a research team that looks at your answers to those questions and combines you with tens of thousands, sometimes hundreds of thousands of other people's answers, and we look for new genetic associations between your survey answers and your genetics. So for the misophonia report in particular, we ask the question, does the sound of other people chewing fill you with rage? Yes, no, or I don't know. And then we looked at people who answered yes or no and just looked to see basically where in their DNA are there differences between people who answered yes and people who answered no. We found there was at least one what we call genetic marker that identifies or that is associated with people who are more likely to say yes. Other people chewing fills me with rage. And we use that to create the mesophonia report. So now people that haven't taken that survey can log on and see, like, do I have the genetic variant that is more associated with being prone to mesophonia?
Adeel [5:33]: Got it. Yeah. And so here's where I get really dumb. So is the gene that's kind of in question called TNM2? Is that the name of the gene that's closest to this marker, I guess?
Alisa [5:49]: Yeah, so the way that works is, so we look at particular locations in your DNA, and we found, like I said, that marker that seems to have, there's a common difference between people, and that difference is associated with mesophonia. Then we can look at what is the nearest gene to that marker, and you're right, it is the TENM2 gene, and that gene is associated with... the formation of neural connections in the brain. Now, something that's really important to note is that just because the genetic marker is near a gene or even in a gene, it doesn't actually mean that it's affecting that gene. It's a good indication, but there's follow-up studies that need to be done to see if this marker actually impacts that gene. But that's the nearest gene to this marker.
Adeel [6:38]: Got it. Okay. So, yeah. So a survey was done and you seem to find a correlation between a similarity around that gene with all these responses indicating misophonia, if I can sum up in a dumb way. So people are voluntarily answering these. And it seemed like, so it looks like about 80,000 people responded. It seemed like for the purposes of the report, You guys selected just people of European descent. And again, is that mainly just because most, probably most consumers were of that descent so that you can get kind of a statistical significant, is that to kind of like rule out any other variants or just curious how you selected who was in the report?
Alisa [7:23]: Yeah, absolutely. So the way these studies are done, they're called genome-wide association studies or GWAS. And essentially what you do is you try and find a population of people that are as similar as possible with the exception of the one thing that you're interested in. So in this case, we're looking at people who are as similar in every way possible except for answering this question around if chewing fills them with rage differently. And so to do that, you need one, a lot of people, and two, a lot of people that are similar to each other. And so typically what we do and what this is standard for all genetic research is to use people of the same sort of ethnic background and the large number of them that you have. So for our database and actually for all the databases out there, this tends to be dominated by people of European descent. So we do have... quite a few people of non-European descent in the database. Unfortunately, we don't have enough of them who have answered the research questions that we can compare just within those different groups. So unfortunately, that's why at this point, the report is most relevant to people just of European descent, although we do provide the report to everyone so they can see if they have that genetic difference. We just aren't quite as sure of how strong that association is with mesothelmia.
Adeel [8:42]: Right. Yeah, that makes total sense. Yeah, it's kind of curious about, yeah, obviously I'm not of European descent. If I log on and it, like, how seriously should I take that result? Well, I guess that needs to be, somebody out there listening should follow on that research, which I guess gets to my earlier point. A lot of this, you don't do this just for misophonia, but a lot of these surveys and reports are... are done proactively to kind of inspire further research, right? Is that kind of one of the main purposes other than spreading the word and raising awareness? Do you have other examples of secondary research coming out that other people have kind of taken the baton and ran with?
Alisa [9:28]: Yeah, so, I mean, your first point about how relevant is this to people of non-European descent, I mean, the main thing that people can do to help us make this most relevant is, again, participate in research. Help us, you know, learn more, especially if people are of non-European descent. That's the most valuable data that we can gather. make this most relevant to the maximum number of people, which is part of our mission. Like I said before, you know, just because we see an association near a gene, we don't know that necessarily means that that gene's impacted. So we love it when, you know, we publish a paper and say, hey, we've seen this association. And then another group goes on and says, okay, cool. Is this really impacting that gene? So, you know, always in science, you want to see studies being reproduced in different databases. And so that's the a goal of ours is to spread the word about what we found to allow more science to happen. So we've seen that with another one of our trait reports where we reported on whether you are more or less likely to notice an interesting odor in your urine after eating asparagus. And amazingly, someone went out and did a follow-up study and replicated that association. So that's one example on the lighter side that we have of people taking our work and moving it forward. But we published over 150 papers on all kinds of different conditions. A lot of that with collaboration with academic or other labs. And so we'd love to see it when other people find similar things to what we do.
Adeel [10:59]: Yeah, then that sounds great. I encourage everyone to stick on 23andMe, spit test or whatever, and to go in and fill out the rest of the questionnaires and for other folks to kind of to try to participate as well. And speaking of like, so you guys do this test, this report internally, is there like a internal or external like review process or what kind of, you want to talk through kind of some of the research standards that you try to maintain or try to follow?
Alisa [11:24]: Yeah, absolutely. So there's a couple things in that question. So one is we have some reports that are meet standards set out by the FDA. And so those reports, we have, we use external literature to identify the associations that we're going to provide. And so those reports have clinical validity that we report on and is public information. And that just means like, hey, this genetic variant is associated with this condition that we're telling people about. We also have analytical validity studies that we do, which basically means that if we're saying, you know, location two in your genome, you have an A instead of a T there, that we have done studies to show that we're greater than 99% accurate in reporting that. And then we also do user comprehension studies for those reports where we show people the reports before they are released. And we show that, again, we have greater than 90% comprehension on what we're presenting to users. So those reports that are about generally more serious health conditions go through that process. And that is all, we talk about that process on our website or through the FDA. Some of the reports that we have that are generally lighter topics, like our trait reports, that's something that the FDA does not regulate. It's not sort of under their purview. And so a lot of that is more based on internal research. And so for that, we do have some white papers that are publicly available on our website about the internal process that we go through to review those reports. But generally, there is a scientific review where we have a team of PhD researchers who look through the proposed report, the proposed association, and evaluate whether that association looks And then we also have internal medical and regulatory folks who evaluate the consumer-facing reports as well.
Adeel [13:22]: Gotcha. Okay. Yeah. Yeah. That, uh, that reminds me that there's, I guess there's a couple of different kinds of reports that 23andMe does. Um, I think they're separated by like either health or wellness, like, and the misophonia one, uh, I believe falls under kind of the wellness side where it's, um, where it was just trying to find, trying, trying to find traits, um, whereas health might be, I don't know, like your, your likelihood to get diabetes or cancer or something. Um, Are those the ones that are more FDA regulated versus these kind of, quote unquote, lighter wellness ones?
Alisa [13:54]: Yeah, generally, it's not always a super clean split like that. But in general, our traits and wellness reports are, like you said, a little bit lighter, but I still think very impactful and very interesting for people to receive. And it really provides an entryway for people to learn more about both their genetics and science and research in general. And then there are the more serious health conditions where those tend to be more deregulated.
Adeel [14:20]: So this report was done, I guess, 2011 or 12, I believe. Is there talk of maybe doing ongoing updates or some kind of update in the future with, because I'm assuming people are answering these questions every day. Is there kind of like a version two that we can maybe expect or 1.2 kind of thing?
Alisa [14:40]: So we have tons of data, which is quite amazing. I mentioned, you know, people that have the option to participate in research and about 80% of our customers do that so like you said we are getting tons of data every day so we do have sort of a balance of how we sift through that data and make decisions around which reports to update or publications to publish i do take a look at our database and you're right since we have launched this report we've done maybe 10 times the amount of data so i think there is the ability for us to go back and see if there's anything any new associations that we we can now find with Generally, the more people you have, the more associations you can find. And we try and update reports whenever they meet our standards. So if we get new data and we have the opportunity to look at that, then we try and do that.
Adeel [15:32]: Right. But yeah, I would imagine it's a lot of work to kind of like for each of these reports. And so you kind of have to plan out when, if and when you want to, you want to go through all that again.
Alisa [15:41]: Each are lovingly crafted.
Adeel [15:43]: Oh yeah, no, they are. Yeah. And that's, I'm going to leave a link to either, even the most technical part of the remote is it's, it's, it's good to read for even the lay person. Yeah. Really interesting and well-written. and and i guess um so some some things people some things people ask and i know you probably this is probably something that's uh another group needs to kind of fall upon but people ask like is there a link to autism with misophonia now this is probably it's not in the report but this is this kind of a natural thing that people would uh that another research group should kind of like uh potentially investigate
Alisa [16:18]: Yeah, so to my knowledge, I don't think we've investigated internally any link between autism and misophonia. I think that's another, that would be a great research project for hopefully other groups and something that maybe we'd be able to collaborate with as we do collect some data like that. But yeah, to my knowledge, I don't think we've looked that up.
Adeel [16:39]: Right. And actually, yeah, on the matter of collaboration, you know, if if if since you have so much more data, you know, if it doesn't if it's maybe not on your roadmap is what kind of ways and there might be researchers listening, like what are some ways that you potentially could collaborate with other groups? Is there kind of a process to do that?
Alisa [16:59]: Yeah, I'm not personally on the research team, so I don't have all the details, but we do have rounds of open calls for collaboration with academics and other groups. So that happens either once or twice a year where basically we will put out a call and researchers can propose a collaboration with us and we evaluate that. Another thing to note about our research is that it is regulated by an IRB, which is an institutional review board that essentially assures that human subjects are treated ethically. And so, you know, we look at the research proposals, make sure our IRB would, that the proposals would meet our standards for that, in addition to our scientific standards. And then if those collaborations sort of make sense, I think they usually go forward.
Adeel [17:50]: Gotcha. Okay, yeah, that's interesting. Hopefully somebody will take you guys up on that. So it sounds like a lot of people are contributing to the survey now. Let's talk about maybe privacy for those folks who might kind of be on the fence on whether it's safe to answer these questions. Do you want to maybe talk a little bit about how you guys kind of anonymize and aggregate data and how that all gets used?
Alisa [18:15]: Sure. And again, I'm not our privacy expert, but I can give sort of the overview. So one important thing that I mentioned is that participating in research is completely an opt-in process. So it's something that if you don't do anything, we do not use your data at all. So if you do choose to opt-in, there's an initial level of opt-in where you basically agree to use your data, but only if it's aggregated and anonymized. So what that means is we would never use your data, your genetic data, in addition to, say, your name or any other identifying features that would allow someone to link basically your genetics to you as a person. So we aggregate things. That's why we, you know, with the Museophonia report, had 80,000 people participating. So, you know, once you get down to You know, 17,000 people saying, you know, yes, chewing fills me with rage. You can't really identify which of those 17,000 people, you know, any individual is. So that's the initial level of consent that people provide. And one way that we protect data is by doing that anonymization and aggregation of data. We also have some people really do want to contribute to deeper level research and they have a rare condition and they want to, you know, say that it's okay actually to share that individual level data, and so there's actually a deeper level of consent. But some people choose to allow for that individual level data to be used, but that's completely up to the individual. We also allow you to change your consent at any time. So if you, this is through the 23andMe website, so you can log in. and see your consent status. So say I chose to participate in research and decided maybe I don't want to anymore, I can change my consent status and say, nope, don't use my data anymore. And obviously, we can't pull you out of any existing studies that have already happened or been published, but your data won't be used going forward. And you can swap back and forth as many times as you want. So we really believe deeply that your data is your own for you to control. you know, we allow you to participate or not in research. And that doesn't impact the service that you receive for us in terms of the reports that you get.
Adeel [20:27]: Gotcha. Okay. And the question that you're asking now about misophonia, is it the same as the original one? It looks like the question is, does the sound of other people chewing for you with rage? And then there's kind of a yes, no, and not sure. Has it been revised over time? I don't know, to add like a scale or something, or is it you're trying to kind of keep it consistent?
Alisa [20:48]: Yes, it's definitely important for us to keep the data consistent. That way we can, you know, look at people who answered the question 10 years ago versus now. Something that we sometimes do, although I don't believe we have specifically for musophonia, is then produce follow-up surveys. So, you know, maybe for migraines or for musophonia, we'd be able to do something like what specific triggers trigger musophonia for an individual who does say yes to that. So that's one way that we can update the survey and hopefully recontact people who have who have told us they have misophonia, if we would choose to do deeper research.
Adeel [21:21]: Gotcha. And have people, like, are people able to change their answers over time? I'm just wondering, you know, has there been more awareness or has people have, and people with misophonia tend to kind of, like, have triggers that, the number of triggers kind of increase over time. I'm just curious if you're able to notice or people have kind of... updated their answers over time?
Alisa [21:43]: So I don't know overall if the answers have updated in the database, but yes, an individual is able to go in and through the research side of the website, they can search for any question that they've answered previously and update or change their answers. So yeah, it's definitely something that you may not get asked again without going in, but if you think, hey, you know, I called 23andMe that I don't have misophonia, but I just started noticing this, then you could definitely go back in and change your answer.
Adeel [22:11]: That's really interesting. And I hope folks listening will either read the report, contribute to the research, or hopefully carry the research forward. Do you have anything else you want to tell folks about 23andMe or this report?
Alisa [22:27]: Sure, yeah. I think this report is a great example of how anyone can be a scientist. Even if you don't have mesophonia, we can use you as a control. Even if you are non-European, especially if you're a non-European, this is one way that you can contribute to scientific research. The 23andMe mission is to help people access, understand, and benefit from the human genome. you know by providing us with research data we can provide you back with hopefully really cool reports like this and hopefully raise awareness about a condition that people might not know so i think it's a really hopefully virtuous cycle that we're always really excited about and it's quite amazing what kind of research that we're able to do just through people like everyone out there just helping us out of the goodness of their hearts. It's pretty great.
Adeel [23:16]: Yeah. I'd like to just thought of one more thing. I know it's around science fair time at my daughter's school. So if any students are looking for something to talk about, this would be, this report would be a great thing to also raise awareness. Well, great. Yeah. Thanks. Thanks, Dr. Lehman. This, this, I know a lot of people have been waiting to hear more about this. So thanks again.
Alisa [23:35]: Absolutely. Thank you for having me.
Adeel [23:37]: Hope you enjoyed that conversation. Definitely check out, again, the show notes and read the papers from 23andMe about misophonia. And one more time, I want to really thank Dr. Elisa Lehman and the entire team at 23andMe for helping me put this together. I'm so grateful when busy people from the research community take the time out to talk to me and talk to the entire audience about misophonia. It really gives us hope to see that people are taking misophonia seriously and doing really good research to help find treatments and potentially a cure. So thank you again. I'd love to keep the conversation going, so please reply to this on social media. We're on Twitter at Misophonia Show and on Instagram at Misophonia Podcast. If you have any questions or comments, they'll be seen by our audience and 23andMe, other researchers. I'd love to hear what your misophonia report says from 23andMe. And if you're a researcher, I'd love to hear if you're following up on any of the results published by 23andMe. If you'd like to help the podcast, please leave a quick rating or even a review in iTunes. It helps get the podcast up in the algorithm and reach more people like you. Other ways to support the show are emailing me to get stickers. Email hello at mrsfunnypodcast.com. I'll send them anywhere in the world for free. Or check out shop.mrsfunnypodcast.com for all kinds of shirts, bags, mugs, and more. This week's theme music is by Moby. And until next week, wishing you peace and quiet.
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