With the world still feeling the effects of the pandemic, the <a href="https://www.ashg.org/meetings/2021meeting/">annual meeting of the American Society of Human Genetics</a> will yet again be virtual this year.
Last year’s conference showed that yes, it was possible to bring together thousands of scientists through their computer screens alone. From October 18th to October 22nd, scientists will virtually gather again for a week of presentations on the latest breakthroughs in genetics.<img loading="lazy" decoding="async" src="https://blog-api.23andme.com/wp-content/uploads/2020/04/cropped-23ANDME-LOGO.jpg" alt="" class="alignright wp-image-28236 size-medium" width="300" height="300" srcset="https://blogcms.23andme.com/wp-content/uploads/2020/04/cropped-23ANDME-LOGO.jpg 300w, https://blogcms.23andme.com/wp-content/uploads/2020/04/cropped-23ANDME-LOGO.jpg 150w, https://blogcms.23andme.com/wp-content/uploads/2020/04/cropped-23ANDME-LOGO.jpg 270w, https://blogcms.23andme.com/wp-content/uploads/2020/04/cropped-23ANDME-LOGO.jpg 192w, https://blogcms.23andme.com/wp-content/uploads/2020/04/cropped-23ANDME-LOGO.jpg 180w, https://blogcms.23andme.com/wp-content/uploads/2020/04/cropped-23ANDME-LOGO.jpg 32w, https://blogcms.23andme.com/wp-content/uploads/2020/04/cropped-23ANDME-LOGO.jpg 512w" sizes="auto, (max-width: 300px) 100vw, 300px" />
<h6>Diversity in Genetics Research</h6>
This year’s <a href="https://www.ashg.org/publications-news/newsletter/20210922-president/">Presidential Symposium</a> will feature a series of talks on diversity, race, inclusion and equity. We’ve previously highlighted 23andMe’s efforts to make our research and product more equitable, and we look forward to learning from others in the field about how we might further improve along with the rest of the broader genomics community.
<h6>23andMe Research Presentations</h6>
The conference will include a broad range of research across the field of genomics. Several scientists from 23andMe will also be presenting some of our related research. This includes our latest research on rare diseases, a recent study of gene expression in blood of individuals of African ancestry, and improved methods for polygenic risk scores.
Here is a list of 23andMe’s presentations and posters:
<ul>
<li aria-level="1"><a href="https://blog.23andme.com/23andme-research/rare-disease-research/">Suyash Shringarpure</a>, PhD, Sr. Scientist I, Statistical Genetics</li>
<ul>
<li aria-level="2">Talk: “<a href="https://eventpilotadmin.com/web/page.php?page=Session&#038;project=ASHG21&#038;id=P1310">Novel genetic associations for rare diseases with GWAS and trans-ethnic analysis of self-reported medical data</a>”</li>
<li aria-level="2">Tue, Oct 19; 4:00pm &#8211; 4:15pm ET</li>
</ul>
<li aria-level="1"><a href="https://blog.23andme.com/therapeutics/kipper-fletez-brant/">Kipper Fletez-Brant</a>, PhD, Scientist II, Computational Biology</li>
<ul>
<li aria-level="2">Poster: <a href="https://eventpilotadmin.com/web/page.php?page=Session&#038;project=ASHG21&#038;id=odP3106&#038;title=Related%20Sessions">“Black Representation in Genomics Research (BRGR) Study of eQTLs in venous blood of 23andMe research participants with African ancestry”</a></li>
<li aria-level="2">Mon, Oct 18; 5:30-6:30pm ET</li>
<li aria-level="2">PrgmNr 3700<div id="attachment_29289" style="width: 1034px" class="wp-caption aligncenter"><img loading="lazy" decoding="async" aria-describedby="caption-attachment-29289" src="https://blog-api.23andme.com/wp-content/uploads/2021/10/BRGR-ASHG-Poster-Kipper-1024x576.jpg" alt="" class="wp-image-29289 size-large" width="1024" height="576" srcset="https://blogcms.23andme.com/wp-content/uploads/2021/10/BRGR-ASHG-Poster-Kipper-1024x576.jpg 1024w, https://blogcms.23andme.com/wp-content/uploads/2021/10/BRGR-ASHG-Poster-Kipper-300x169.jpg 300w, https://blogcms.23andme.com/wp-content/uploads/2021/10/BRGR-ASHG-Poster-Kipper-768x432.jpg 768w, https://blogcms.23andme.com/wp-content/uploads/2021/10/BRGR-ASHG-Poster-Kipper-880x495.jpg 880w, https://blogcms.23andme.com/wp-content/uploads/2021/10/BRGR-ASHG-Poster-Kipper-1180x664.jpg 1180w" sizes="auto, (max-width: 1024px) 100vw, 1024px" />Kipper&#8217;s ASHG poster detailing preliminary data from the BRGR study.</div></li>
</ul>
<li aria-level="1">Jingchunzi Shi, PhD, Scientist II, Statistical Genetics</li>
<ul>
<li aria-level="2">Poster: “<a href="https://eventpilotadmin.com/web/page.php?page=Session&#038;project=ASHG21&#038;id=P3291">Improving Polygenic Risk Score Transferability by Leveraging GWAS Signals from Diverse Populations</a>”</li>
<li aria-level="2">Mon, Oct 18; 5:30-6:30pm ET</li>
<li aria-level="2">PrgmNr 3885<div id="attachment_29293" style="width: 970px" class="wp-caption aligncenter"><img loading="lazy" decoding="async" aria-describedby="caption-attachment-29293" src="https://blog-api.23andme.com/wp-content/uploads/2021/10/ASHG2021_Multi_Population_PRS-.jpg" alt="" class="wp-image-29293 size-full" width="960" height="540" srcset="https://blogcms.23andme.com/wp-content/uploads/2021/10/ASHG2021_Multi_Population_PRS-.jpg 960w, https://blogcms.23andme.com/wp-content/uploads/2021/10/ASHG2021_Multi_Population_PRS--300x169.jpg 300w, https://blogcms.23andme.com/wp-content/uploads/2021/10/ASHG2021_Multi_Population_PRS--768x432.jpg 768w, https://blogcms.23andme.com/wp-content/uploads/2021/10/ASHG2021_Multi_Population_PRS--880x495.jpg 880w" sizes="auto, (max-width: 960px) 100vw, 960px" />Jingchunzi&#8217;s ASHG poster on improving polygenic risk scores for diverse populations.</div></li>
</ul>
</ul>
You can find out more about this years ASHG meeting <a href="https://www.ashg.org/meetings/2021meeting/">here</a>.

23andMe Blog

23andMe Blog Team

23andMe at ASHG 2021

Kipper Fletez-Brant, a computational biologist with our Therapeutics division, thought he’d be a physicist one day.
<img loading="lazy" decoding="async" src="https://blog-api.23andme.com/wp-content/uploads/2021/09/kipper_pic_2-196x300.jpg" alt="" class="alignright wp-image-29155 size-medium" width="196" height="300" srcset="https://blogcms.23andme.com/wp-content/uploads/2021/09/kipper_pic_2-196x300.jpg 196w, https://blogcms.23andme.com/wp-content/uploads/2021/09/kipper_pic_2-768x1176.jpg 768w, https://blogcms.23andme.com/wp-content/uploads/2021/09/kipper_pic_2-669x1024.jpg 669w, https://blogcms.23andme.com/wp-content/uploads/2021/09/kipper_pic_2-575x880.jpg 575w, https://blogcms.23andme.com/wp-content/uploads/2021/09/kipper_pic_2-771x1180.jpg 771w, https://blogcms.23andme.com/wp-content/uploads/2021/09/kipper_pic_2.jpg 1288w" sizes="auto, (max-width: 196px) 100vw, 196px" />Growing up in Phoenix, Arizona, Kipper escaped the heat reading “hard-sci-fi novels” with mind-bending plots woven with currently understood science about things like dark matter, wormholes, and the bending of the space-time continuum.
“But I realized at some point I liked living things and physics wasn&#8217;t the best fit,” he said.
Physics is sometimes referred to as the philosopher’s science. So perhaps it was appropriate that instead of a hard science, Kipper tackled other kinds of hard questions and studied philosophy as an undergraduate at St. John’s College.
After four years of wrestling with the eternal questions of life, he wanted something different.
“I wasn&#8217;t keen on the fact that there aren&#8217;t answers in philosophy,” Kipper said.
And that in turn motivated him to “think about science again.”
After graduation, while doing clerical work for an ophthalmologist, a doctor who noticed his aptitude and interest suggested he consider bioinformatics.
“I learned that was a way to put math and biology together,” Kipper said. “There was just one catch. I hadn’t studied either.”
It’s what motivated him to go back to school and break into the field. What followed was a Masters in Biotechnology giving him crash courses in computer science and molecular biology. He went on to work in a genetics lab and then spent time at the <a href="https://www.niaid.nih.gov/about/vrc">National Institutes of Health’s Vaccine Research Center</a>, working on data related to vaccine trials. Work that he’s been thinking about on a daily basis since the pandemic.
“Our mission was to understand, on a molecular level, what changes vaccines caused, so that we could make better, more effective vaccines,” Kipper said. 
The mission was important but Kipper wanted to lead research himself, and so he returned to school, but this time for a Ph.D. in Human Genetics from the <a href="https://www.hopkinsmedicine.org/institute-genetic-medicine/">McKusick-Nathans Institute of Genetic Medicine</a> at Johns Hopkins University’s School of Medicine and a Masters in Statistics from the School of Public Health.
Now three years into his work at 23andMe, Kipper is a critical part of the team of scientists and computational biologists looking for potential drug targets. One of the projects that Kipper is working on is a research effort called the<a href="https://blog.23andme.com/23andme-research/black-representation-in-research/"> Black Representation in Genomic Research Study</a> (BRGR) in which scientists are studying the genetics of gene expression with the aim of improving diversity in biomedical research. Ultimately, the aggregated and de-identified RNA and whole-genome sequencing data from the project will be made available to qualified researchers through the NIH’s dbGap. The hope is that this will assist those developing more effective drugs that can treat conditions and diseases affecting members of the Black community who have been underrepresented in traditional research.
It’s just one of many examples of what excites Kipper about working at 23andMe. For a scientist still fascinated by the potential of genetics to lead to novel therapies, he said being part of <a href="https://therapeutics.23andme.com/">23andMe’s Therapeutics </a>division offers rare opportunities.
“The genetic and phenotypic data at 23andMe is unparalleled,” Kipper said. “There is simply no other resource that compares to the 23andMe database in terms of the scale of phenotypes surveyed or size of the cohort.”
As part of an occasional series about scientists working at 23andMe, we sat down with Kipper to talk more about computational biology, 23andMe, and what it’s like being a scientist in 23andMe’s Therapeutics division.
<h6>Where did you grow up?</h6>
I grew up in Phoenix, AZ. I remember when it hit 122F in the early 90s. It grounded airplanes, many people had heatstroke. We didn&#8217;t have AC at the time, so my mom sprayed us with the hose (this motivated my parents to get AC)
<h6>What did you study as an undergrad?</h6>
I studied philosophy at St. John&#8217;s College, a small liberal arts college in Annapolis, Maryland. (It is directly across the street from the United States Naval Academy).
<h6>Did you always want to be a scientist?</h6>
Intermittently. As a child, I thought I might want to do physics because I read a lot of &#8220;hard&#8221; sci-fi where they talked about the physics of things like space travel. But I realized at some point I liked living things and physics wasn&#8217;t the best fit. I did philosophy because at least I thought about difficult things a lot, but I wasn&#8217;t keen on the fact that there aren&#8217;t answers in philosophy, which motivated me to think about science again.
<h6>Was your interest inspired by a person or a book or an experience?</h6>
After undergrad, I was working as an administrative assistant in a North Baltimore suburb for an ophthalmology office, and one of the doctors told me I should look at bioinformatics. I learned that was a way to put math and biology together. The catch was I hadn’t studied either. But that motivated me to look around for ways to break into the field.
<h6>Why did you get two master’s degrees (in Statistics and Biotechnology) and was there something that changed to prompt you to get your Ph.D. in human genetics?</h6>
I somehow talked my way into my first masters, in Biotechnology at Johns Hopkins, despite having a degree in philosophy and no scientific training. I was essentially making up for lost time. I studied computer science and molecular biology during this degree, while also interning as a laboratory technician in a molecular genetics lab. It really set me up for success, and after graduating I took a job as a data analyst at the National Institutes of Health’s (NIH) Vaccine Research Center, mainly working on datasets that came from participants in vaccine trials. Our mission was to understand, on a molecular level, what changes vaccines caused so that we could make better, more effective vaccines.
<h6>Why did you leave the NIH?</h6>
While the NIH was a great job with really smart people, I knew I wanted to lead research projects, and I did not have the training for that. I also missed working in genetics and genomics, and so I enrolled in the Human Genetics program at the McKusick-Nathans Institute of Genetic Medicine at the Johns Hopkins University School of Medicine. While there, I knew I needed serious training in statistics to match the biological training from my Ph.D. program, so I did my Ph.D. work with Kasper Hansen, a professor in the Department of Biostatistics in the School of Public Health, and also did a master&#8217;s degree in biostatistics. In addition, I was a fellow of the Maryland Genetics, Epidemiology and Medicine (MD-GEM) training program, where I also trained in genetic epidemiology. 
<h6>What are the kinds of questions or problems you like to study?</h6>
I really like difficult problems that don’t have clear answers and make you think in several disciplines at once. At the NIH, I developed a tool for doing quality control of vaccine data that uses statistical concepts typically used in geology. While a Ph.D. student, I worked on statistical methods to find genetic variants that impact what 3D structure DNA actually takes when it is in a cell.
<h6>What attracted you to working for 23andMe’s Therapeutics team?</h6>
At the NIH I was working very closely with clinical research, and I knew that after my Ph.D. I wanted to return to more translational work. 23andMe, where everything is based on genetics, was a natural choice for me. And to date, I have used every part of my training, from molecular genetics to epidemiology to statistics, to answer questions about how to take our genetic findings and identify drug targets using them. 
<h6>Could you explain a little bit about your job analyzing functional genomics data and how it plays a role in characterizing potential drug targets?</h6>
At 23andMe, everything we do starts with genetics.  We know which genetic variants are associated with which diseases. The problem is that knowing that some genetic variant is associated with a disease often tells you nothing about how the variant causes disease, nor what you might do about it. The Computational Biology group helps generate ideas about how diseases are caused by genetic variation, and which genes might be good drug targets, by using our genetic data in conjunction with other biological data, such as the gene expression profiling we did in the BRGR study. Specifically, we often ask questions about whether particular variants affect the expression or function of possible target genes — maybe a particular gene is over-expressed in some diseases with an unmet medical need, for example.
<h6>What is unique about working at 23andMe either in terms of the kind of data you’re working with or the culture?</h6>
The genetic and phenotypic data at 23andMe is unparalleled. There is simply no other resource that compares to the 23andMe database in terms of the scale of phenotypes surveyed or the size of the cohort. Many GWAS that we run yield signals seen in no other cohort. In this context, drug development is very exciting, in that how to use genetic information to hone in on a drug target is a topic of active research in the community. 23andMe Therapeutics is breaking ground on hard questions and is one of the leaders in this space.
<h6>How is what you’re doing now different from what you were doing at St. Johns, or different from other jobs you’ve had?</h6>
My role at 23andMe is closer to the drug/therapeutic development process than any other job I’ve had, which was a huge draw for me, to be honest. At Johns Hopkins, I worked on questions that were focused on understanding basic biology, and at the NIH I was downstream of the development process. Here I am actively helping the Therapeutics team find new targets.
<h6>What are your hopes for the work you are doing?</h6>
I am optimistic that we will find “the best” way to use genetics to inform drug discovery. Our comprehensive dataset allows us to target a wide variety of diseases, and I am hopeful we can make an impact on many of them and the lives of people living with those diseases.

Tackling Tough Problems with the 23andMe Therapeutics Team

Xin Fang’s interest in science started at the dinner table, listening to her parents talking about what they did each day. 
Both her mom and dad are plant scientists. Her mom focuses on genetics, and her father on the environment. They worked long hours, but they would come home enthused. And, sitting with her parents at the table for the family meal, Xin listened as her mom and dad engaged in conversations about the latest discoveries made or problems solved. It fascinated her.<img loading="lazy" decoding="async" src="https://blog-api.23andme.com/wp-content/uploads/2021/09/XinFang1-200x300.jpg" alt="" class="alignright wp-image-29144 size-medium" width="200" height="300" srcset="https://blogcms.23andme.com/wp-content/uploads/2021/09/XinFang1-200x300.jpg 200w, https://blogcms.23andme.com/wp-content/uploads/2021/09/XinFang1-683x1024.jpg 683w, https://blogcms.23andme.com/wp-content/uploads/2021/09/XinFang1-587x880.jpg 587w, https://blogcms.23andme.com/wp-content/uploads/2021/09/XinFang1-787x1180.jpg 787w, https://blogcms.23andme.com/wp-content/uploads/2021/09/XinFang1-768x1152.jpg 768w, https://blogcms.23andme.com/wp-content/uploads/2021/09/XinFang1-scaled.jpg 1706w" sizes="auto, (max-width: 200px) 100vw, 200px" />
<h3>The Wonders of Human Biology</h3>
Now a computational biologist in 23andMe’s Therapeutics division, Xin said her parents’ passion for science fueled her own ambition. By high school she knew she wanted to be a scientist, she just wasn’t sure about her path. Moving from China to the United States to attend Johns Hopkins University, Xin studied chemical and biomolecular engineering. It was there that her interest in bioinformatics took root. She was fascinated by the “mystery of the human body and how it works,” she said. Xin was sucked into the fact that data and bioinformatics offered a door to understanding parts of the mystery of human biology.
“I love the fact that we can develop new techniques to understand the mechanisms behind human biology,” Xin said.
Now a little over a year into her work at 23andMe, Xin is deep into collaborating with fellow computational biologists and bench scientists to help find potential drug targets to pursue. Computational biology, data science, and machine learning play a critical role in 23andMe’s drug discovery process. Our scientists have the great fortune of gleaning insights from what is one of the largest genetic and phenotypic datasets in the world.
For Xin, the attraction of coming to work at 23andMe wasn’t just that she’s interested in genetics or that she sees the promise of 23andMe’s data helping to accelerate the development of new treatments, it’s also because drug discovery at 23andMe is driven by data, which allows computational biologists like her to propose new research directions and make major contributions. The size and scale of our dataset enables rapid discoveries.
As part of an occasional series about scientists working at 23andMe, we sat down with Xin to talk about computational biology, 23andMe, and what it’s like being an early career scientist here.
<h6>Did you always want to be a scientist?</h6>
Pretty early on I did. By high school, I knew I wanted to do something in biochemistry but I wasn’t sure what.
<h6>Was your interest in science inspired by a person or an experience?</h6>
Definitely it came from my parents. They were both scientists and very passionate about it, and it had a great impact on me. They worked a lot but they were happy about what they were doing. We spent a lot of hours talking about their work over dinner.
<h6>You studied chemical and biomolecular engineering at Johns Hopkins, what prompted you to do your doctoral work in bioengineering?</h6>
I took a gap year working at Genentech after my undergraduate studies. That and my experience during undergrad helped me realize that I was more interested in bioinformatics and computational modeling.
Consider the human body. It’s this perfect mystery that it works in a way that it does, and we don’t totally understand it. But when you bring in high-throughput data, especially from large genomics datasets or next-generation sequencing, you start to see more clearly different biological mechanisms at play. That’s the most fascinating part. And I love that we can use these new techniques and assays to try and understand it. It’s just awesome.
<h6>Why did you focus on studying the gut microbiomes and IBD during your doctoral work at UCSD?</h6>
The gut microbiome is a significant part of our body but it hasn’t been well understood before. It interacts with the rest of the human body in a lot of different ways including things like exchanging metabolites and breaking down medicines. And in recent years it has been discovered that the gut microbiome is associated with several diseases and inflammatory bowel disease (IBD) is one of them.  Basically, what you observe is an imbalance in the microbiome where there is a reduction in the beneficial microbes but an increase in pathogens. My thesis looked at characterizing if there are any specific pathogens associated with developing inflammatory bowel disease. The second part of what I did was to look at how the microbiome could affect the treatment for IBD.
<h6>What attracted you to working for 23andMe’s Therapeutics team?</h6>
I was a 23andMe customer even when I was a broke Ph.D. student. And I’m in bioinformatics and a huge fan of genetics. I’ve always been a strong believer that personal genetics is going to make its way into modern medicine, and become a part of standard practice.
So, when I was looking for a job, 23andMe was a company I was really interested in. But to be honest I didn’t know much back then about 23andMe’s Therapeutics program. I didn’t know about 23andMe’s unique approach to target discovery or the drug pipeline. It wasn’t really until the interview and until I had the opportunity to talk to the Computational Biology team that I fully understood what the Therapeutics program was about and it was really exciting.
A major advantage we have is the size of our database. And this is extremely important in terms of discovery because we have better power to detect genetic signals useful for identifying drug targets that other databases can’t. And of course, our data comes from customers who consented to participate in research and who we can contact in the future if we need to. So, that’s another advantage. 
<h6>Describe a little bit about some of what you do in your day-to-day work.</h6>
I can divide my current role into two different aspects that support our therapeutics discovery and development process. The first is to help with data analysis in support of identifying biomarkers that could be useful for clinical trials. I am also working on developing automatic reports for later stage programs. 
And the second part of my job is more upstream, on integrating different datasets to improve the variant (GWAS hit) to target gene mapping process. We want to identify genes that are actually affecting the disease and understand the mechanism of action.
<h6>What’s different about working here?</h6>
For me, I guess what influenced my decision to come here is that 23andMe is doing genetics-based, data-driven discovery. So as part of the Computational Biology team, you can make major contributions to drug discovery whereas in a more traditional biotech/pharma setting Computational Biology would play much more of a supporting role.
As a scientist, I am very interested in doing research and exploratory projects that are intellectually challenging and at 23andMe we have the opportunity to do these things.
<h6>How have you managed your work-life balance over the last year during the pandemic?</h6>
I’m working primarily from home but I go to the office two or three times a week. At first, it was hard because I started at 23andMe during the shelter in place while we were all working from home. But the team has been really good about meeting each week and making sure questions are answered so I don’t feel like I’m by myself all the time. And there is a good work-life balance.
<h6>What interests you outside of work?</h6>
I used to play a lot of badminton. I actually trained for it as a kid, but stopped playing in grad school and shifted over to table tennis. In the office we have a table tennis tournament going on after the work hours, so that’s fun. And during the pandemic, I got a puppy so that’s occupying my time right now too.

Helping to Drive Discovery in 23andMe’s Therapeutics Division

Among his many jobs as 23andMe senior scientist in statistical genetics, Suyash Shringarpure, Ph.D. leads some of our rare disease discovery and prediction work.
But since first coming here in 2016, he’s been involved in a wide variety of projects all leaning on his extensive background in machine learning. Suyash came here after doing post-doctoral work in Carlos Bustamante’s Lab at Stanford University where he worked on genetic data privacy, ancestral inference, and next-generation genetic sequencing. He received his Ph.D. in Machine Learning from Carnegie Mellon University, and he received his undergraduate degree in Computer Science and Engineering from the Indian Institute of Technology in Bombay.
<div id="attachment_28941" style="width: 228px" class="wp-caption alignright"><img loading="lazy" decoding="async" aria-describedby="caption-attachment-28941" src="https://blog-api.23andme.com/wp-content/uploads/2021/06/©PITER2017Suyash-Shringarpure2649-218x300.jpg" alt="" class="wp-image-28941 size-medium" width="218" height="300" srcset="https://blogcms.23andme.com/wp-content/uploads/2021/06/©PITER2017Suyash-Shringarpure2649-218x300.jpg 218w, https://blogcms.23andme.com/wp-content/uploads/2021/06/©PITER2017Suyash-Shringarpure2649-768x1056.jpg 768w, https://blogcms.23andme.com/wp-content/uploads/2021/06/©PITER2017Suyash-Shringarpure2649-745x1024.jpg 745w, https://blogcms.23andme.com/wp-content/uploads/2021/06/©PITER2017Suyash-Shringarpure2649-640x880.jpg 640w, https://blogcms.23andme.com/wp-content/uploads/2021/06/©PITER2017Suyash-Shringarpure2649-858x1180.jpg 858w, https://blogcms.23andme.com/wp-content/uploads/2021/06/©PITER2017Suyash-Shringarpure2649-scaled.jpg 1862w" sizes="auto, (max-width: 218px) 100vw, 218px" />Suyash Shringapure, Ph.D., a 23andMe senior scientist, and statistical geneticist.</div>
There’s a lot we could talk about because his work touches so many parts of the company — from research and development for our health product team, to work in support of Therapeutics, to some of the backend technical efforts related to things like the phasing of genetic data. But we sat down, virtually, to talk to Suyash specifically about his work on rare diseases at 23andMe. This is one in an occasional series we’ve been doing over the last few months looking at rare diseases. Suyash recently spoke about his research at the National Press Foundation as part of <a href="https://hopin.com/events/rare-and-mystery-diseases">a session on rare diseases</a>. (We will post a recording of the session when it becomes available.) 
In the spring we published new research led by Suyash looking specifically at the unique way 23andMe can<a href="https://blog.23andme.com/23andme-research/new-way-to-study-rare-disease/"> study rare diseases.</a> It offered some unexpected insights into these hard-to-study conditions.
“This approach will enable us to discover new genetic associations across multiple populations much faster than could be done otherwise,” he said at the time.
Read on to find out more about what he had to say:
<h6>Even before you came to 23andMe, you were known for using machine learning and statistical methods for work on a broad range of different scientific problems. Why is machine learning such a powerful tool in genetics and biology and for the study of disease?</h6>
Genetics has become a data-rich field in the last couple of decades. There are now many large human genetic (and gene expression etc.) datasets available for researchers. Because the genetic risk for most common diseases is an aggregate of many different genetic variants — sometimes hundreds even thousands of variants — machine learning and statistical methods offer a powerful tool in calculating disease risk. In genetics and biology, these algorithms can infer the small contributions of many genetic variants and combine them appropriately to describe disease risk.
<h6>Why are you and other scientists at 23andMe so interested in rare diseases, and why are we studying<a href="https://www.23andme.com/systemic-sclerosis-study/"> systemic sclerosis</a>, and<a href="https://www.23andme.com/idiopathic-pulmonary-fibrosis/"> idiopathic pulmonary fibrosis (IPF)</a> in particular?</h6>
Though each rare disease only affects a small number of people, there are nearly 7000 known rare diseases, and the total number of people affected by rare diseases is quite large. It’s estimated that about 20-25 million Americans and 300 million people worldwide are living with a rare disease. In addition, about 70 percent of all rare diseases are genetic, while only 5 percent of all rare diseases have approved treatments. So there is a large unmet need for therapeutics for rare diseases, which is why we at 23andMe are so interested. Beyond the need, our large database is also well-suited for studying rare diseases. It’s often difficult to study rare diseases because it is a challenge to find enough individuals to participate in research. But 23andMe now has enough people who have consented to participate in research that we can more quickly gather enough individuals with a specific rare disease to find statistically robust genetic associations.
Idiopathic pulmonary fibrosis (IPF) is a life-threatening, progressive lung disease with a median survival of three to five years after diagnosis. The genetics of IPF is not well-understood, and at present, there are only two FDA-approved therapies, and unfortunately, neither is always well-tolerated by patients. We believe we can use our research model to find insights into the disease, and that’s why we started our <a href="https://www.23andme.com/idiopathic-pulmonary-fibrosis/">IPF Study</a>.
Similar to IPF, Systemic sclerosis is a rare disease for which there is an unmet need for treatments. Systemic sclerosis is an autoimmune disease that affects the skin and internal organs, and we don’t fully understand the genetics of the disease.  Much like with our IPF Study, we launched our <a href="https://www.23andme.com/systemic-sclerosis-study/">Systemic Sclerosis Study</a> to better understand the genetics of the condition and to improve our ability to discover new genetic associations for these diseases.   
<h6>You completed an <a href="https://blog.23andme.com/23andme-research/new-way-to-study-rare-disease/">interesting study</a> using 23andMe’s unique research model to study rare diseases. Were those findings a surprise when you made them?</h6>
Some of them were definitely a surprise. We have lots of experience in studying common diseases, where we need to have tens of thousands of affected individuals in our study to find statistically significant genetic associations. It was a surprise for us when we were able to find genetic associations in studies of rare diseases with only tens of affected individuals. Another surprise was finding that common genetic variants show association with rare disease risk. Previously, it has been found that rare genetic variants cause rare diseases, so this was unexpected. Unsurprisingly, we found that similar regions of the genome contribute to risk in different populations and that aggregating data across all populations enables us to make the most discoveries. 
<h6>What makes 23andMe’s research model unique for studying rare diseases?</h6>
The main bottleneck in studying rare diseases is finding enough people with the condition to participate in the research. 23andMe’s large research-consented cohort means that even for a disease that affects one-in-100,000 people, we can find nearly 100 affected individuals for our analysis. The self-reported data-collection model we have also allowed us to study thousands of diseases at once, rather than studying one disease at a time. So for example, in the study we just published on the preprint server <a href="https://www.medrxiv.org/content/10.1101/2021.06.09.21258643v1">MedRxiv</a>, we did genome-wide association studies (GWAS) on 33 different rare diseases. For three of those rare diseases, our GWAS was the first-ever done on those conditions. So the unique features of 23andMe’s research database allowed us to find the results included in our study. Another unique feature is that through additional surveys, we can also find associations of rare diseases with other traits/diseases. For example, <a href="https://blog.23andme.com/23andme-research/insights-from-ipf-study/">early insights</a> from our IPF study show that IPF patients are more likely to report having gastrointestinal reflux, shortness of breath, depression, and anxiety. 
<h6>What are you currently working on?</h6>
On the rare disease front, we are continuing to recruit IPF and Systemic sclerosis patients for our ongoing studies. We are also studying genetic associations for more diseases, as our cohort keeps growing. Outside of that, my team and I are working on trying to improve disease risk prediction, specifically on how to make genetic risk predictions accurate for all populations, and how to combine genetic and non-genetic data for risk prediction.
<h6>Have you learned anything interesting from your own 23andMe results?</h6>
I’ve never been a regular coffee drinker, even in graduate school, when many people are heavy coffee drinkers. Turns out I’m genetically less likely than average to drink caffeine, according to my 23andMe Caffeine  Consumption Wellness report! 
 
&nbsp;

Talking About Rare Disease with Senior Scientist Suyash Shringarpure

By Daniella Coker, MPH, and Janie Shelton, Ph.D.*
Several studies show the three COVID-19 vaccines being used in the United States — from Johnson &amp; Johnson (J&amp;J), Moderna, and Pfizer — are safe<a href="https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/safety-of-vaccines.html">1,</a>2 and effective2,<a href="https://www.cdc.gov/coronavirus/2019-ncov/vaccines/effectiveness/work.html">3</a>  and offer the best hope to beat the pandemic.2,4 And as so many of us have gotten vaccinated, it’s impossible not to notice that people react differently to the vaccines. Many people report having no reaction, while others feel sick enough to stay home in bed. 23andMe researchers wanted to know more about why. Is it due to the type of vaccine, our age, or something else?
To learn more about these differences we analyzed the data from more than 100,000 23andMe consented research participants and found that the second in the two-shot vaccine from Moderna produced the strongest reactions. We also learned that younger people and women tended to react more to the vaccine than others.
<h2>Get Vaccinated</h2>
But before going into what our researchers found, we should be clear: The side effects of vaccines are minimal, while the risks from the virus caused by COVID-19 are severe. This was further confirmed by new <a href="https://www.cdc.gov/mmwr/volumes/70/wr/mm7032e4.htm?s_cid=mm7032e4_w">data from the CDC</a>.  More than 35 million people in the United States have contracted the virus caused by COVID-19, and 614,000 of them have died. Even with the emerging Delta variant cases, the most significant risk is remaining unvaccinated. We encourage people to take the advice of healthcare professionals, the <a href="https://www.who.int/emergencies/diseases/novel-coronavirus-2019/covid-19-vaccines/advice">World Health Organization</a>, state and local public health officials, and the CDC and get vaccinated. 
23andMe’s researchers wanted to examine differences in how sick people felt after receiving the vaccines. Now that more than half the U.S. population has been fully vaccinated and about 60 percent have had at least one shot,<a href="https://covid.cdc.gov/covid-data-tracker/#vaccinations">5</a> our scientists wanted to explore how people react differently to different vaccines and what factors may influence those differences. This study does not look at adverse reactions but categorizes how people felt after they were vaccinated and compares the degree of “feeling sick” between three different vaccines.
For 23andMe’s study, consented research participants were asked three questions: (1) What was their most recent COVID-19 vaccination? (2) What symptoms, if any, did they experience? and (3) How sick did they feel afterward.
Most research participants reported that their most recent vaccination was their second dose of either the Pfizer (44%) or Moderna (38%) vaccine.

 <figure class="wp-block-image size-large is-style-default"><img loading="lazy" decoding="async" width="260" height="167" src="https://blogcms.23andme.com/wp-content/uploads/2021/08/sample-size.png" alt="" class="wp-image-29110"/></figure>
 
Approximately half of respondents didn’t feel sick, 40% felt a little or somewhat ill, and 10% felt very or extremely sick. And to be clear, “feeling sick” as a reaction to the shot is not the same as being clinically sick from the virus and requiring hospitalization. 23andMe scientists sought to describe and characterize this wide range of reactions to the COVID-19 vaccines.
Here are some of the key findings:
<h2>The second Moderna shot seemed to produce the strongest reactions</h2>
Compared to the other vaccines, it was those people with a second dose Moderna vaccination who most often reported experiencing any symptoms (85%), and most often reported feeling either very or extremely sick (18%) after their vaccination. Again, these differences were not related to clinical outcomes. In other words, these are relatively modest reactions to the vaccines, but the vaccines still offered strong protection against the virus. In addition, these reactions were generally only for a couple of days after the vaccination. Whereas the severity of COVID-19 infections includes potential weeks or months of hospitalization or death. In addition, scientists still don’t fully know the timeline for so-called COVID-19 “longhaulers,” people dealing with lingering symptoms long after being infected.

 <figure class="wp-block-image size-large is-style-default"><img loading="lazy" decoding="async" width="512" height="314" src="https://blogcms.23andme.com/wp-content/uploads/2021/08/vaccine-reaction-by-type.png" alt="" class="wp-image-29111" srcset="https://blogcms.23andme.com/wp-content/uploads/2021/08/vaccine-reaction-by-type.png 512w, https://blogcms.23andme.com/wp-content/uploads/2021/08/vaccine-reaction-by-type-300x184.png 300w" sizes="auto, (max-width: 512px) 100vw, 512px" /></figure>
 
Fatigue, pain at the injection site, and muscle/body aches were the most commonly reported symptoms for all vaccine types. Yet, for every symptom (except nausea), a larger portion of Moderna’s second-dose recipients reported experiencing that symptom compared to recipients of other vaccines.

 <figure class="wp-block-image size-large is-style-default"><img loading="lazy" decoding="async" width="512" height="106" src="https://blogcms.23andme.com/wp-content/uploads/2021/08/vaccine-matrix.png" alt="" class="wp-image-29112" srcset="https://blogcms.23andme.com/wp-content/uploads/2021/08/vaccine-matrix.png 512w, https://blogcms.23andme.com/wp-content/uploads/2021/08/vaccine-matrix-300x62.png 300w" sizes="auto, (max-width: 512px) 100vw, 512px" /></figure>
 
And in logistic regression models controlling for key demographics (age, sex, BMI, ethnicity, education, and history of COVID-19 infection), having received a second Moderna shot was significantly associated with 3x odds of experiencing any symptom and nearly 1.5x odds of feeling very or extremely sick (as compared to J&amp;J).
So, you are not imagining things &#8212; if you got the Moderna 2nd dose and felt “under the weather”, you are not alone. A lot of people did (nearly 1 in 5), but for <a href="https://www.cdc.gov/vaccines/covid-19/info-by-product/moderna/moderna-faqs.html#vaccine-safety-efficacy">94.1% effectiveness</a> against COVID-19, we are all applauding those of you who suffered through a few days of discomfort for your and the greater good.
<h2>A history of COVID-19 infection associated with feeling sicker </h2>
You may have heard the rumor that people who have had COVID-19 are more likely to feel sick after receiving a vaccine. According to 23andMe data, that seems to be true — a larger proportion of consented research participants previously infected with COVID-19 reported feeling sick for every degree of sickness (from “a little” to “extremely”) compared to those not previously infected with COVID-19. In fact, only a third of participants with a previous infection experienced no symptoms from their vaccine, compared to half of those without a COVID-19 history.

 <figure class="wp-block-image size-large is-style-default"><img loading="lazy" decoding="async" width="512" height="285" src="https://blogcms.23andme.com/wp-content/uploads/2021/08/How-Sick-do-you-feel.png" alt="" class="wp-image-29113" srcset="https://blogcms.23andme.com/wp-content/uploads/2021/08/How-Sick-do-you-feel.png 512w, https://blogcms.23andme.com/wp-content/uploads/2021/08/How-Sick-do-you-feel-300x167.png 300w" sizes="auto, (max-width: 512px) 100vw, 512px" /></figure>
 
Even after controlling for the key demographic variables listed above, having a history of a COVID-19 infection increased your odds of experiencing any symptoms or feeling very/extremely sick after your vaccination, both by about 30%.
<h2>More and stronger reactions for women and younger individuals</h2>
Women were more likely to have any symptoms, have more whole body (systemic) symptoms, and generally feel sicker following their vaccination compared to men.  

 <figure class="wp-block-image size-large is-style-default"><img loading="lazy" decoding="async" width="512" height="314" src="https://blogcms.23andme.com/wp-content/uploads/2021/08/vaccin-reaction-by-sex.png" alt="" class="wp-image-29114" srcset="https://blogcms.23andme.com/wp-content/uploads/2021/08/vaccin-reaction-by-sex.png 512w, https://blogcms.23andme.com/wp-content/uploads/2021/08/vaccin-reaction-by-sex-300x184.png 300w" sizes="auto, (max-width: 512px) 100vw, 512px" /></figure>
 
In fact, after controlling for potential confounders, women were almost twice as likely as men to have felt very or extremely ill.
Similar trends were observed for younger individuals when compared to older folks. Those 40 years of age and younger experienced between 2 and 3 whole-body symptoms on average, and nearly a quarter felt very or extremely sick. By contrast, those at least 75 years old experienced between 0 and 1 whole-body symptoms on average, and only 4% felt very ill.

 <figure class="wp-block-image size-large is-style-default"><img loading="lazy" decoding="async" width="512" height="315" src="https://blogcms.23andme.com/wp-content/uploads/2021/08/vaccine-reaction-by-age.png" alt="" class="wp-image-29109" srcset="https://blogcms.23andme.com/wp-content/uploads/2021/08/vaccine-reaction-by-age.png 512w, https://blogcms.23andme.com/wp-content/uploads/2021/08/vaccine-reaction-by-age-300x185.png 300w" sizes="auto, (max-width: 512px) 100vw, 512px" /></figure>
 
These relationships between sex, age, and vaccine reaction held up, even after controlling for potential confounders.
<h2>How do the COVID-19 vaccines work?</h2>
The COVID vaccines teach your immune system to recognize and respond to the virus that causes COVID-19. The vaccines introduce genetic instructions to make a harmless protein that is unique to the virus. This triggers a two-step immune response: a first, more immediate and non-specific reaction (the innate immune response), followed by a more gradual, pathogen-specific reaction (the adaptive immune response).<a href="https://www.healio.com/hematology-oncology/learn-immuno-oncology/the-immune-system/the-innate-vs-adaptive-immune-response">6</a>
But why do some people feel very sick from their COVID-19 vaccine, and others don’t feel sick at all? Scientists aren’t quite sure why that is. However, data points to the immune system.
<h2>What does my vaccine reaction mean?</h2>
Trends identified in 23andMe data support what the vaccine clinical trials and other studies have observed — that certain groups of people are more likely to have felt sicker from their COVID-19 vaccination. These include:
<ul>
<li aria-level="1">Women<a href="https://www.cdc.gov/mmwr/volumes/70/wr/mm7008e3.htm">7</a></li>
<li aria-level="1">Younger people<a href="https://www.cdc.gov/mmwr/volumes/70/wr/mm7008e3.htm">7,</a> 8,9,<a href="https://www.cdc.gov/vaccines/covid-19/info-by-product/janssen/reactogenicity.html">10</a></li>
<li aria-level="1">Recipients of a second dose vaccine (compared to their first dose)8,9,<a href="https://jamanetwork.com/journals/jama/fullarticle/2778441">11</a></li>
</ul>
Women, for instance, seem to have stronger immune reactions than men. Research for other types of vaccinations, such as for influenza, yellow fever, and hepatitis, showed that women produce more infection-fighting antibodies than men following vaccination.<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438701/">12</a> Hormonal and genetic differences between the sexes may also play a role in how the immune systems of men and women respond differently to vaccinations. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438701/">12,</a><a href="https://www.sciencedirect.com/science/article/pii/S1028455920302175">13</a>
As we age, our immune systems tend to weaken.<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3901832/">14</a> This may explain why younger adults were generally more likely to report a larger number of and more severe symptoms following their vaccination compared to older adults, as seen in data from 23andMe consented research participants and elsewhere, including the vaccines’ clinical trials.<a href="https://www.cdc.gov/mmwr/volumes/70/wr/mm7008e3.htm">7,</a>8, 9, <a href="https://www.cdc.gov/vaccines/covid-19/info-by-product/janssen/reactogenicity.html">10</a>
By the time you receive a second dose, your body has already become primed to recognize and respond to the virus that causes COVID-19, and as a result your immune system responds faster and stronger. <a href="https://www.gavi.org/vaccineswork/why-vaccine-side-effects-might-be-more-common-people-whove-already-had-covid-19">15,</a><a href="https://www.nationalgeographic.com/science/article/why-vaccine-side-effects-really-happen-and-when-you-should-worry">16</a> This likely explains why people tend to have more severe reactions to their second dose compared to their first dose.
And it may also be why 23andMe researchers observe that people with a history of COVID-19 infection also feel more ill following their most recent vaccination, compared to those without a prior infection. The virus itself is an additional trigger for your immune responses to kick in. Several small studies have found that people with a history of COVID-19 infection experienced symptoms more frequently<a href="https://www.medrxiv.org/content/10.1101/2021.01.29.21250653v1">17,</a><a href="https://covid.joinzoe.com/post/vaccine-after-effects-more-common-in-those-who-already-had-covid">18 </a>and had higher levels of antibodies after a first dose,<a href="https://jamanetwork.com/journals/jama/fullarticle/2777171">19</a> compared to those without a history of infection.
This analysis on over 100,000 individuals builds upon these findings, showing that a previous COVID-19 infection might not just be related to the number of symptoms experienced following a COVID-19 vaccination, but also the severity of these symptoms.
<h2>The COVID-19 vaccines are still effective, regardless of your vaccine-related reaction</h2>
Although there is some uncertainty regarding why some people experience more mild or severe symptoms following their COVID-19 vaccination, what we do know is this: the COVID-19 vaccines are effective, whether or not you felt sick after the vaccination.
Data from the vaccine trials showed that not everyone reported vaccine-related reactions; 23% from Pfizer, 18% from Moderna (second dose), and between 39% (younger adults) and 55% (older adults) from J&amp;J didn’t experience any systemic reactions.8,9,<a href="https://www.cdc.gov/vaccines/covid-19/info-by-product/janssen/reactogenicity.html">10</a> And this is coming from the same data that demonstrated how safe and effective these vaccines are.
Put another way: “Even if you don’t have an unpleasant reaction, the vaccines are still doing their job, because the real work of the immune system &#8211; and of the vaccines &#8211; takes place during the second, or adaptive phase of the immune response.”<a href="https://www.nationalgeographic.com/science/article/why-vaccine-side-effects-really-happen-and-when-you-should-worry">16</a>
<h2>What’s next?</h2>
Research is ongoing to understand why reactions to the COVID-19 vaccines differ and what these differences mean.  This work is part of our ongoing broad research into COVID-19 that has included studying how genetics plays a role in both the <a href="https://www.nature.com/articles/s41588-021-00854-7">susceptibility and severity of COVID-19</a> and looking at other aspects of the pandemic like its impact on <a href="https://blog.23andme.com/23andme-research/covid-impact-on-sleep/">sleep</a>, <a href="https://blog.23andme.com/23andme-research/stepping-back-up-amid-covid-19/">physical activity</a> and how it has <a href="https://blog.23andme.com/23andme-research/impact-disparities-of-covid-19/">hit some communities harder than others</a>. As part of this work, our scientists are preparing to run genetic analyses to help answer why individuals react differently to the vaccine and what those differences might mean.
<hr />
*The 23andMe COVID-19 research team includes Adam Auton, Adrian Chubb, Alison Fitch, Alison Kung, Amanda Altman, Andy Kill, Anjali Shastri, Antony Symons, Catherine Weldon, Chelsea Ye, Jason Tan, Jeff Pollard, Jey McCreight, Jess Bielenberg, John Matthews, Johnny Lee, Lindsey Tran, Maya Lowe, Michelle Agee, Monica Royce, Nate Tang, Pooja Gandhi, Raffaello d’Amore, Ruth Tennen, Scott Dvorak, Scott Hadly, Stella Aslibekyan, Sungmin Park, Taylor Morrow, Teresa Filshtein Sonmez, Trung Le, and Yiwen Zheng.

A logo for 23andMe's COVID-19 Research Study

COVID-19 Vaccine Reaction Data

For the uninitiated the mere idea of smearing a sticky blackish sludge of brewer&#8217;s yeast on a piece of toast and then eating it for breakfast might trigger a wee bit of nausea, and yet there are people in this world who love Marmite.
Why?
<h6>Taste Preference</h6>
Like many of the other <a href="https://www.bbc.co.uk/programmes/b007zpll">Big Questions</a> we face in this life, the answer is complicated. And then there&#8217;s the fact that Marmite is one of those polarizing foods you either love or hate. 
We&#8217;re into science, and we like to ask probing and even provocative questions here at 23andMe. So we wanted to know if we could learn a little about whether genetics might play a role in your choice of breakfast spreads. <img loading="lazy" decoding="async" src="https://blog-api.23andme.com/wp-content/uploads/2021/08/Marmite-300x220.png" alt="Pieces of toast with Marmite spread over them." class="alignright wp-image-29103 size-medium" width="300" height="220" srcset="https://blogcms.23andme.com/wp-content/uploads/2021/08/Marmite-300x220.png 300w, https://blogcms.23andme.com/wp-content/uploads/2021/08/Marmite-768x562.png 768w, https://blogcms.23andme.com/wp-content/uploads/2021/08/Marmite-1024x750.png 1024w, https://blogcms.23andme.com/wp-content/uploads/2021/08/Marmite-880x644.png 880w, https://blogcms.23andme.com/wp-content/uploads/2021/08/Marmite-1180x864.png 1180w" sizes="auto, (max-width: 300px) 100vw, 300px" />
Genetics, after all, factors into our taste preferences.  Whether it&#8217;s liking <a href="https://blog.23andme.com/health-traits/traits-never-looked-better/">Salty v. Sweet</a> snacks, or have an aversion to <a href="https://blog.23andme.com/health-traits/traits-never-looked-better/">Bitter Taste</a>, or a dislike of <a href="https://blog.23andme.com/health-traits/23andme-adds-four-new-trait-reports/">Cilantro</a>, your genes pay at least a small role. And don&#8217;t get us started on &#8220;<a href="https://blog.23andme.com/health-traits/tasty-genetics/">supertasters</a>.&#8221; These kinds of culinary inclinations are determined by a complex interaction between your environment, your lifestyle, and, yes, your DNA. 
So what about Marmite? (We&#8217;re going to leave Vegemite, Marmite&#8217;s even more robust Aussie cousin, in the pantry for now.)
<h6>What About the Genetics?</h6>
Genetics explains some of the appeal of Marmite, according to a new genome-wide association study by researchers at 23andMe. 
Looking at data from more than 100,000 23andMe customers of European descent who consented to participate in research — and who know what the heck Marmite is — Peter Chisnell, PhD., a 23andMe Health R&amp;D scientist found three genetic variants associated with &#8220;loving&#8221; Marmite. 
In follow-up analysis, Peter looked at the area in the genome where we saw the strongest genetic association. It is near a gene related to olfaction, a key to our sense of taste. The SNP is near the <a href="https://www.ncbi.nlm.nih.gov/gene/6496">SIX3 gene</a>, a &#8220;homeobox protein,&#8221; and acts like a master controller for the expression and regulation of a bunch of genes. 
“It&#8217;s a giant sledgehammer kind of gene that affects a lot of things,&#8221; said Peter. 
<h6>Smell and Taste</h6>
Large changes in its function have been shown to disrupt neurodevelopment in mice, including a part of their brain responsible for olfaction. We don&#8217;t really know exactly how these small genetic changes in people could explain differences in taste, but it’s plausible that changes in the sense of smell may make one more prone to like the salty savory flavor of Marmite. 
Along with the association found near the SIX3 homeobox gene, the study found an association near the gene OR12D1, an olfactory receptor. Finally, Peter’s analysis noted a significant single nucleotide polymorphism (SNP) associated with loving Marmite near the NRXN3 gene, which is involved in the nervous system, including behavioral traits like fear and empathy, but also tendencies toward addiction and obesity. 
What these all may or may not mean regarding a preference toward the salty-savory taste of Marmite is about as opaque as the dark syrupy spread itself. After all, our sense of taste is a complex process. 
Taste receptors on our tongue bind to a set of chemical compounds in food to recognize specific odorants or tastants and then sends that information to our brains. There are receptors for five types of tastes — sweet, sour, salty, bitter, and savory, also known as umami. Several different genes are essential for taste and smell. So, for example, the TAS1R and TAS2R gene group is involved in the perception of sweet, umami, and bitter perception. The hundreds of genes that are part of the olfactory receptor gene group also play a role. 
<h6>The Cultural Story </h6>
Beyond the biology involved in taste is a whole slew of cultural and environmental factors that go into what each of us likes and doesn&#8217;t like to eat. 
We see a little of that in 23andMe&#8217;s study because we also looked beyond genetics. The 23andMe researchers broke down individuals by sex and also by country, not just where they currently reside but where they were born. Men were more likely to love Marmite than women, for instance. The difference between men and women isn&#8217;t likely explained by the genetic associations we analyzed, Peter said. The data also gets interesting when you break it down geographically. 
This offers a great example of how culture also plays a role in taste preference. Genetics can&#8217;t really explain the differences in why some countries have more Marmite lovers than others. This is because countries have about the same proportion of people who are genetically predisposed to liking Marmite.
As you would expect, the researchers found that most people who knew about Marmite lived in Commonwealth countries with strong ties to the UK. And unsurprisingly, some of those same countries were where you found the most Marmite lovers — New Zealand, South Africa, Australia, and the UK. But also among the countries that ranked highest for loving it were Russia and Turkey.
Among those places that ranked highest for hating Marmite were the US, Canada, and Ireland.
&#8220;We don&#8217;t have a great biological mechanism to explain those differences,&#8221; said Peter. &#8220;The cultural story seems more plausible to me than a biological explanation.&#8221;
<h6>An Acquired Taste</h6>
Food preferences and acquired tastes are greatly influenced by the culture we live in. 
And why do you have more Marmite haters in Canada, Ireland, and the US? There are no discernable genetic differences to explain that. 
Interestingly, none of the genetic associations we found for loving Marmite were in the genes associated with bitter taste receptors. Nor did we replicate any of the associations in the only other genome-wide association study on Marmite. 
And yes, our GWAS is actually not the first one on Marmite. A few years back, the company that has made the spread since the first World War launched the <a href="https://www.marmite.co.uk/the-gene-project.html">Marmite Gene Project</a>. In collaboration with another company, they ran a <a href="https://www.dnafit.com/downloads/MarmiteGenetics_WhitePaper_Final.pdf">GWAS using just 261</a> people. That tiny study found 15 SNPs associated with Marmite preference. But the researchers acknowledged that the study lacked statistical power. None of the SNPs or genes identified in that study were replicated in our own.
&nbsp;

A black and white image of toast with Marmite spread on it

The Genetics of Loving or Hating Marmite

By Alexa Reynoso, 23andMe Associate Scientist, Genetic Epidemiology
The use of electronic cigarettes, or vaping, is associated with several unhealthy behaviors and traits particularly among young people, according to new data from 23andMe.
But the data merely notes an association between vaping and those behaviors and traits, it’s not an indication of causation. Unlike the long-established research that links smoking to cancer, disability, and death, there remains a dearth of data on the health effects of vaping. Some recent studies have linked vaping to deleterious effects on the lungs. And last year a Stanford study found an association between<a href="https://www.jahonline.org/article/S1054-139X(20)30399-2/fulltext#secsectitle0050"> risk for COVID-19 and vaping</a> among young people.
<h2>Health Impacts</h2>
Scientists are still at the beginning of understanding the long-term health implications of e-cigarettes. At 23andMe we’ve only been collecting data on vaping for about a year. In the summer of 2020, our researchers added new questions to our smoking survey to account for vaping and e-cigarette use.
By looking at data we’ve gathered from the more than 76,000 customers who consented to participate in research and responded to our smoking survey, we were able to explore demographic and other characteristics of e-cigarette users. We were then able to compare people who vape to those who smoke just cigarettes, or who both smoke and vape (dual users), and those who don’t smoke or vape at all. (Note: This is not a representative sample of the entire 23andMe population, nor is it representative of national numbers. The CDC estimates that 4.5 percent of adults in the United States vape.¹ Among 23andMe research participants, only about .2 percent, or 19,000 individuals, reported being regular e-cigarette users. The sample for this research is composed only of respondents to our Smoking survey.)

 <figure class="wp-block-image size-large is-style-default"><img loading="lazy" decoding="async" width="1024" height="683" src="https://blogcms.23andme.com/wp-content/uploads/2021/08/GettyImages-975633438-1024x683.jpg" alt="" class="wp-image-29075" srcset="https://blogcms.23andme.com/wp-content/uploads/2021/08/GettyImages-975633438-1024x683.jpg 1024w, https://blogcms.23andme.com/wp-content/uploads/2021/08/GettyImages-975633438-300x200.jpg 300w, https://blogcms.23andme.com/wp-content/uploads/2021/08/GettyImages-975633438-768x512.jpg 768w, https://blogcms.23andme.com/wp-content/uploads/2021/08/GettyImages-975633438-880x587.jpg 880w, https://blogcms.23andme.com/wp-content/uploads/2021/08/GettyImages-975633438-1180x787.jpg 1180w" sizes="auto, (max-width: 1024px) 100vw, 1024px" /></figure>
 
<h2>What are E-Cigarettes?</h2>
Before we get into what the data showed, it’s worth understanding a bit more about how e-cigarettes work.
Introduced in 2004,² e-cigarettes were first touted as a less harmful way for smokers to kick their habit. Unlike with cigarettes, users of e-cigarettes are not inhaling smoke. They are inhaling a smoke-like aerosol, or vapor, produced when these devices heat a liquid that usually contains nicotine but also other potentially harmful substances.¹
While vaping may be helping some who are trying to kick their smoking habit, it may also be a gateway for others starting a nicotine addiction. This could be particularly relevant for young people. Juul Labs recently paid a $40 million settlement to the state of North Carolina for allegedly targeting youth in its marketing. According to a study on vaping trends published last year in the<a href="https://www.nejm.org/doi/full/10.1056/NEJMc1910739"> New England Journal of Medicine</a>, it was noted that an increase in vaping among young people between 2018 and 2019 was “the largest of any substance tracked” in the last four decades.
<h2>23andMe’s Data on Vaping Among Young People</h2>
In looking at our data, 23andMe researchers found that those between the ages of 18-30 were more likely to vape.

 <figure class="wp-block-image size-large is-style-default"><img loading="lazy" decoding="async" width="512" height="385" src="https://blogcms.23andme.com/wp-content/uploads/2021/08/Figure-1-E-cigs.png" alt="" class="wp-image-29097" srcset="https://blogcms.23andme.com/wp-content/uploads/2021/08/Figure-1-E-cigs.png 512w, https://blogcms.23andme.com/wp-content/uploads/2021/08/Figure-1-E-cigs-300x226.png 300w" sizes="auto, (max-width: 512px) 100vw, 512px" /></figure>
 
Not only were young people more likely to vape, but these younger users of e-cigarettes were also more likely to use them at a higher frequency. Essentially, they take more “puffs” each day than older people in the study who vape. These findings are in accordance with those of the CDC.¹
Beyond being younger, individuals who are dual users — they smoke and vape — come from locations with a slightly lower median household income when compared to cigarette-only users, e-cigarette only users, and those that used none. Lastly, when comparing the four use groups in regards to years of education, research participants that do not smoke or vape tend to have obtained the highest amount of education.
Our researchers also stratified by sex and ethnicity but did not find strong differences as they did with age.
<h2>23andMe Insights</h2>
While we did not look specifically at health outcomes, we did look at various associations with unhealthy behavior and traits.
We found associations between vaping and such things as being more likely to be stressed, depressed, and anxious compared to those who do not vape. People who vape also were more likely to be diagnosed with bi-polar disorder. We saw associations between people who vape being more likely to report poor overall health, low life satisfaction as well as being less likely to exercise and eat right. People who vape in our data also were more likely to eat less fruit, drink more caffeine, need higher doses of pain medication, and are less likely to be a morning person. (More associations found with e-cigarette use within the 23andMe database are summarized in Figure 1. )

 <figure class="wp-block-image size-large is-style-default"><img loading="lazy" decoding="async" width="512" height="418" src="https://blogcms.23andme.com/wp-content/uploads/2021/08/E-cig-associations.png" alt="" class="wp-image-29096" srcset="https://blogcms.23andme.com/wp-content/uploads/2021/08/E-cig-associations.png 512w, https://blogcms.23andme.com/wp-content/uploads/2021/08/E-cig-associations-300x245.png 300w" sizes="auto, (max-width: 512px) 100vw, 512px" /></figure>
 

 <figure class="wp-block-image size-large is-style-default"><img loading="lazy" decoding="async" width="1024" height="564" src="https://blogcms.23andme.com/wp-content/uploads/2021/08/Table-1-E-Cigs-1024x564.png" alt="" class="wp-image-29095" srcset="https://blogcms.23andme.com/wp-content/uploads/2021/08/Table-1-E-Cigs-1024x564.png 1024w, https://blogcms.23andme.com/wp-content/uploads/2021/08/Table-1-E-Cigs-300x165.png 300w, https://blogcms.23andme.com/wp-content/uploads/2021/08/Table-1-E-Cigs-768x423.png 768w, https://blogcms.23andme.com/wp-content/uploads/2021/08/Table-1-E-Cigs-880x485.png 880w, https://blogcms.23andme.com/wp-content/uploads/2021/08/Table-1-E-Cigs-1180x650.png 1180w, https://blogcms.23andme.com/wp-content/uploads/2021/08/Table-1-E-Cigs-271x149.png 271w, https://blogcms.23andme.com/wp-content/uploads/2021/08/Table-1-E-Cigs-372x204.png 372w, https://blogcms.23andme.com/wp-content/uploads/2021/08/Table-1-E-Cigs-574x315.png 574w, https://blogcms.23andme.com/wp-content/uploads/2021/08/Table-1-E-Cigs-980x539.png 980w, https://blogcms.23andme.com/wp-content/uploads/2021/08/Table-1-E-Cigs.png 1274w" sizes="auto, (max-width: 1024px) 100vw, 1024px" /></figure>
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An environment-wide association study of cigarette smokers in our database was also conducted to determine if there are any fundamental differences between research participants that smoke e-cigarettes versus tobacco cigarettes.
<h2>Correlations</h2>
Our results indicated that the two groups are much more similar than they are different. Similar to the e-cigarette results, we saw that smokers were much more likely to experience depression and anxiety. Both cigarette and e-cigarette users also reported a lower general health score. Other interesting correlations (see Figure 2.) were that cigarette smokers tend to drink more alcohol  and tend to be more hot-headed.

 <figure class="wp-block-image size-large is-style-default"><img loading="lazy" decoding="async" width="512" height="414" src="https://blogcms.23andme.com/wp-content/uploads/2021/08/E-cigs-associations-2.png" alt="" class="wp-image-29094" srcset="https://blogcms.23andme.com/wp-content/uploads/2021/08/E-cigs-associations-2.png 512w, https://blogcms.23andme.com/wp-content/uploads/2021/08/E-cigs-associations-2-300x243.png 300w" sizes="auto, (max-width: 512px) 100vw, 512px" /></figure>
 

 <figure class="wp-block-image size-large is-style-default"><img loading="lazy" decoding="async" width="1024" height="395" src="https://blogcms.23andme.com/wp-content/uploads/2021/08/Table-2-E-cigs-1024x395.png" alt="" class="wp-image-29093" srcset="https://blogcms.23andme.com/wp-content/uploads/2021/08/Table-2-E-cigs-1024x395.png 1024w, https://blogcms.23andme.com/wp-content/uploads/2021/08/Table-2-E-cigs-300x116.png 300w, https://blogcms.23andme.com/wp-content/uploads/2021/08/Table-2-E-cigs-768x297.png 768w, https://blogcms.23andme.com/wp-content/uploads/2021/08/Table-2-E-cigs-880x340.png 880w, https://blogcms.23andme.com/wp-content/uploads/2021/08/Table-2-E-cigs-1180x456.png 1180w, https://blogcms.23andme.com/wp-content/uploads/2021/08/Table-2-E-cigs.png 1274w" sizes="auto, (max-width: 1024px) 100vw, 1024px" /></figure>
 
Although researchers uncovered correlations between smoking and certain demographic variables, it should be noted that correlation does not equal causation. Proving that certain behaviors or demographics cause another is quite difficult; meaning that we can’t say if someone isn&#8217;t a morning person they must be an e-cigarette user. In order to come to these conclusions, researchers must conduct years of extensive research consisting of numerous rigorous trials and studies.
That’s not to say what we uncovered so far is trivial, but rather we are on the right track. We are still just beginning to understand the long-term health implications of e-cigarettes. Over time, however, with the power of our large research cohort and scientific community, we could uncover more novel associations between e-cigarette use and long-term health effects.
23andMe customers who would like to contribute to our research efforts surrounding e-cigarette usage can take the survey <a href="https://you.23andme.com/research/surveys/tobacco/">here</a>. Not yet a customer? Find out more <a href="https://www.23andme.com/compare-dna-tests/?spt=spt">here</a>.
<hr />
<h2>References</h2>
<ol>
<li>“About Electronic Cigarettes (E-Cigarettes).” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 28 Apr. 2021, www.cdc.gov/tobacco/basic_information/e-cigarettes/about-e-cigarettes.html.</li>
<li>Cobb, Nathan K., et al. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2978165/">“Novel Nicotine Delivery Systems and Public Health: The Rise of the ‘E-Cigarette.’</a>” American Journal of Public Health, vol. 100, no. 12, 2010, pp. 2340–2342., doi:10.2105/ajph.2010.199281.</li>
</ol>

23andMe Looks at Data on E-Cigarette Use

When Melissa Tarantino talks about facing challenges every day to her special needs students at a middle school near Sacramento, they listen. They all are aware that she knows what she&#8217;s talking about.
A former gymnast, Melissa learned at 19 that the pain and numbness in her hands was a symptom of scleroderma, a rare disease that she&#8217;d never heard of before. The diagnosis came after more than a year of being treated, including two surgeries for what doctors thought was carpal tunnel syndrome brought on by her years in gymnastics. It was a heavy diagnosis for someone who was just starting college.
When the doctor gave her the diagnosis, she asked:
&#8220;Will I ever be able to do a cartwheel again?&#8221;
<h6>Cartwheels and Research</h6>
That was eight years ago now. Melissa was able to do cartwheels again, but it hasn&#8217;t been easy.
She recently chatted with 23andMe about how she&#8217;s approached living with scleroderma, a progressively debilitating autoimmune disease that often results in tightening and hardening of the skin, muscle weakness, and pain. The condition affects an estimated <a href="https://worldsclerofound.org/what-is-ss/">2.5 million people</a> globally. Most of those with systemic sclerosis — about 80 percent — are women like Melissa between 16 and 45.
Although there are some treatments for this progressively debilitating autoimmune disease, there currently is no cure. But there is promising research like that being done by 23andMe.
Our conversation with Melissa is one in an occasional series on the blog about rare diseases like scleroderma. You can read some of the other posts about new insights into the <a href="https://blog.23andme.com/23andme-research/new-way-to-study-rare-disease/">study of rare diseases</a>, living with another rare disease idiopathic pulmonary fibrosis, and a discussion with a community engagement director for the <a href="https://blog.23andme.com/23andme-research/scleroderma-research/">Scleroderma Research Foundation</a>. The posts detail studies into rare diseases, as well as two specific studies 23andMe is currently recruiting for — <a href="https://www.23andme.com/idiopathic-pulmonary-fibrosis/">idiopathic pulmonary fibrosis</a>, a chronic progressive lung disease, and <a href="https://www.23andme.com/systemic-sclerosis-study/">systemic sclerosis</a>, a form of scleroderma.
Melissa, who is participating in <a href="https://www.23andme.com/systemic-sclerosis-study/">23andMe&#8217;s Systemic Sclerosis Study</a>, said it&#8217;s important to contribute to the effort.
&#8220;Of course, I&#8217;m participating,&#8221; she said. &#8220;I just want to be able to help in whatever way I possibly can.&#8221;
Here&#8217;s more of what Melissa had to say.
<h6>Many people with a rare disease talk about how difficult it was to simply find the right diagnosis. Was that your experience?</h6>
The backstory is that I’d been a gymnast all my life, from like second grade to senior year of high school. I decided I wanted to stop and be a kid again, you know, go to the prom and not have to train 30 hours a week.
After I stopped, I started noticing pain and numbness in my hands. The doctors thought it was carpal tunnel from all that training, so I had surgery first on one hand and then the other.
My freshman year in college I still had pain, the knuckles in my hands were super swollen and I started to gain weight, then lose it, and I had this bloating in my face. The pain in my hands was really bad. At one point during a history final, it hurt so bad that I was crying. At that point, I went back to the doctor and they still thought the pain was from my time as a gymnast. The doctor told me to take acetaminophen. It was super frustrating.
<h6>What changed?</h6>
I knew something was wrong and my mom knew it too. We switched doctors and got blood work done. Even before the appointment my mom and I looked at the results from the lab work and then sort of self-diagnosed things. We looked up lupus and scleroderma while we sat on the couch. We weren’t 100 percent sure but we kind of pieced things together. We didn’t know anyone who had (scleroderma). We never heard of it before.
But we lucked out and got connected to a good rheumatologist with connections to Stanford who’d actually studied the disease. So, after the first diagnosis, I’ve had good care.
<h6>What were some of the hardest things for you during that time?</h6>
I was in college, and as I said, I wanted to live a college life. I wanted to live my life as a young person. So, at first, I didn’t take all the heavy medications that were prescribed. I let my doctor know. (Among the medication she waited to take was an immunosuppressant methotrexate. She waited to take it because of some of its side effects.)
Like I said I didn’t know anything about scleroderma until we’d Googled it, and everything we read online basically said you die right away. I didn’t have high hopes, but it turns out I won the scleroderma lottery. The kind of scleroderma I have isn’t affecting my internal organs now. Once I had my years in college, I started using the immunosuppressant methotrexate. Maybe I wouldn’t have lost some of the bone that I lost if I’d started taking it during college, but I’m glad I had that time in college to lead a somewhat normal student life.
<h6>What are some of the things you find that help you day-to-day?</h6>
Five years is a big marker for this condition, and I’m now seven or eight years in, and I’m at my healthiest. I now do powerlifting and being active really helps me feel better. You know before I started powerlifting I did tell myself I wanted to prove my doctor wrong.
So, while I was at Sacramento State I joined a gymnastics club and ended up competing in Nationals when they were in Sacramento. I proved that I could do cartwheels. I might have done them a little differently than I did before, but I did them. I did four events. Once I did that, I knew that having a physical outlet was important for me but I needed to shift to something else so that’s when I started powerlifting. 
Powerlifting really helps me release stress. I usually try and go at about 3:30 in the morning before I start my day. When I don’t work out my kids (who she teaches at a middle school in Sacramento) know it, and usually say something.
<h6>How has being involved with different groups such as the Scleroderma Research Foundation helped you?</h6>
Going to their fundraisers or conferences helped me meet more people with the disease who were actually my age. That’s been very helpful for my mental health. I don’t feel alone and I can talk to someone who I can ask about, you know, things like dating or how to deal with changes in your appearance. That kind of stuff has really helped.
<h6>Why are you participating in 23andMe’s Systemic Sclerosis Study?</h6>
Of course, I&#8217;m participating. I&#8217;ve actually tried to participate in other (scleroderma) studies but this is the first I qualified for.
I’m participating in the 23andMe study because I just want to be able to help in whatever way I possibly can. This disease isn&#8217;t going to just go away. I have it for life, so this is something I can do now in my lifetime to help others. It might not make a difference for me but it might for someone in the future.

Living with Scleroderma

A new study that identified genes linked to longer fertility in women comes as data show a sharp decline in birth rates during the pandemic, which accentuated a decades-long trend in women putting off having children until later in life.
<h6>Reproductive Aging</h6>
Published this week in the journal <a href="https://www.nature.com/articles/s41586-021-03779-7">Nature</a>, the study identified about 300 genetic variants that influence longer reproductive lifespan. Beyond simply identifying these genetic variants, the scientists were able to manipulate some of those genes in mice to successfully extend the reproductive lifespan. The findings offer some hope to those studying fertility in women.
“Improved understanding of the biological processes involved in reproductive aging could lead to improvements in fertility treatment options,” said Professor Eva Hoffman of the University of Copenhagen. Hoffman co-authored the new study.
<h6>New Insight for Women</h6>
The study gives a better understanding of the genetic influences for extending reproductive health. But it also also offers insights into identifying which women might reach <a href="https://www.nature.com/articles/d41586-021-01710-8">menopause earlier than other</a>s. This in turn could help those women decide on the timing of when or if to have children.
“We can start to predict which women might have an earlier menopause and therefore struggle to get pregnant naturally,&#8221; said Dr. Katherine Ruth, of the University of Exeter, and a study co-author. &#8220;And because we are born with our genetic variations, we could offer this advice to young women.”
<h6>More Delaying Having Children</h6>
Life expectancy has dramatically gone up over the last century or more. But the age at which women enter menopause — around 50 — has not changed. Women are born with all the eggs they will ever carry. These are gradually lost with age. Menopause occurs once most of a woman&#8217;s eggs are gone.  But fertility declines substantially before that time, making it much more difficult for some women to get pregnant. There are a number of factors playing into the delay in having children including financial and career considerations. According to<a href="https://www.cdc.gov/nchs/data/vsrr/vsrr012-508.pdf"> newly released data</a>, the COVID-19 pandemic resulted in the sharpest drop in childbirth in more than a century.
Many of the genes the study identified are associated with the process of DNA repair and are active before birth when human eggs are created and stored. These include the genes CHEK1 and CHEK2, which regulate a broad variety of DNA repair processes.
“We saw that two of the genes which produce proteins involved in repairing damaged DNA work in opposite ways with respect to reproduction in mice,” said Professor Ignasi Roig. Roig is another of the study&#8217;s co-authors and works at of the Autonomous University of Barcelona.
The researchers found that turning off the function of the gene CHEK2, while enhancing the expression of CHEK1, extended the reproductive lifespan of mice by about 25 percent. The study also looked at women who naturally lack an active CHEK2 gene. They found that these women reach menopause on average 3.5 years later than women with a normally active gene.
For this study, the researchers relied on a global collaboration involving more than 180 academic institutions. The study included data from hundreds of thousands of women. This included 300,000 female customers from 23andMe who consented to participate in research. The researchers also included data from the<a href="https://www.ukbiobank.ac.uk/"> UK Biobank</a> and several other study cohorts. While most of the de-identified and aggregated data was from women of European ancestry, the researchers also looked at data from women of East Asian ancestry.
<h6>Menopause</h6>
The team discovered that many of the genes involved are linked to processes of DNA repair. They also found that many of these genes are active from before birth, when human egg stores are created. But they are also active throughout life as well. Female mice with more of the CHEK1 protein are born with more eggs and they take longer to deplete naturally, so reproductive lifespan is extended. The second gene, CHEK2, has a similar effect. It allows eggs to survive longer, but in this case, the gene has been knocked out so that no protein is produced.”
The team also examined the health impacts of having an earlier or later menopause by using an approach that tests the effect of naturally occurring <a href="https://www.23andme.com/dna-health-ancestry" target="_blank" rel="noopener">genetic differences</a>. They found that genetically earlier menopause increases the risk of type 2 diabetes. It is also linked to poorer bone health and increased risk of fractures. However, it decreases the risk of some types of cancer. This is especially true of some cancers, such as ovarian and breast cancer, that are known to be sensitive to sex hormones. Those hormones are at higher levels in menstruating woman.

Research — Page 14