What stories and breakthroughs shaped the year in science and genetics? 
That was the question we asked a group of 23andMe leaders who are experts in everything from human genetics to product science to diversity, equity, and inclusion.
Their wide-ranging responses span disciplines. You’ll find biology breakthroughs, public health declarations, illuminating visualizations, AI technologies, and rigorous scientific debates. 
COVID-19 is well represented in their answers, too, including new gains in scientific literacy as we continue to add terms like “spike protein” and “T cells” to the lexicon. 
The result is a list that collectively embodies our <a href="https://www.23andme.com/about?bst=pff">core value</a> of scientific discovery and captures a year of progress. 
<h2>Virology, Variants, Vaccines: A New Era of Scientific Literacy </h2>
<a href="https://mediacenter.23andme.com/press-release/23andme-announces-the-appointment-of-joseph-r-arron-m-d-ph-d-as-chief-scientific-officer">Joe Arron</a>, Chief Scientific Officer

 <figure class="wp-block-image size-large is-style-default"><img loading="lazy" decoding="async" width="1024" height="477" src="https://blogcms.23andme.com/wp-content/uploads/2021/12/COVID-Image-1024x477.png" alt="" class="wp-image-29418" srcset="https://blogcms.23andme.com/wp-content/uploads/2021/12/COVID-Image-1024x477.png 1024w, https://blogcms.23andme.com/wp-content/uploads/2021/12/COVID-Image-300x140.png 300w, https://blogcms.23andme.com/wp-content/uploads/2021/12/COVID-Image-768x358.png 768w, https://blogcms.23andme.com/wp-content/uploads/2021/12/COVID-Image-880x410.png 880w, https://blogcms.23andme.com/wp-content/uploads/2021/12/COVID-Image-1180x550.png 1180w, https://blogcms.23andme.com/wp-content/uploads/2021/12/COVID-Image.png 1394w" sizes="auto, (max-width: 1024px) 100vw, 1024px" /></figure>
 
“Any way you slice it, the biggest story of the year — genetic or otherwise — is the coronavirus pandemic. The global scale of COVID-19’s effects on health, politics, economics, and culture is staggering, but observing biology plays out in real-time has been equally staggering. 
I have been struck by the dramatic rise in scientific literacy across our society. This is partly because scientists, journalists, and politicians have worked to understand and explain rapidly changing developments in viral variants, vaccines, antiviral therapies, epidemiology, and public health guidelines. These explanations often use technical molecular terms that have become part of our everyday language. 
For example, soon after the Omicron variant of SARS-CoV2 was discovered and sequenced, you could find visualizations of a <a href="https://www.nytimes.com/interactive/2021/12/14/science/omicron-variant-science.html">molecular model of the spike protein</a> mutations in the media. As an immunologist, it’s gratifying to see both the public’s interest in such things as antibodies, T cells, and viruses, as well as the patience and enthusiasm with which my colleagues endeavor to explain these complex processes in accessible language. 
While we all hope that this pandemic will soon recede into memory, I also hope that our society will remain engaged in seeking a deeper understanding of science, medicine, and the power of genetic technology to benefit human health.” 

<h2>Racism is a Public Health Crisis for Black Americans</h2>
<a href="https://blog.23andme.com/articles/melinda-king/">Melinda King</a>, Director of Diversity, Equity, and Inclusion and People Business Partner

 <figure class="wp-block-image size-large is-style-default"><img loading="lazy" decoding="async" width="1024" height="536" src="https://blogcms.23andme.com/wp-content/uploads/2020/09/DEI-Blog-1024x536.png" alt="" class="wp-image-28515" srcset="https://blogcms.23andme.com/wp-content/uploads/2020/09/DEI-Blog-1024x536.png 1024w, https://blogcms.23andme.com/wp-content/uploads/2020/09/DEI-Blog-300x157.png 300w, https://blogcms.23andme.com/wp-content/uploads/2020/09/DEI-Blog-768x402.png 768w, https://blogcms.23andme.com/wp-content/uploads/2020/09/DEI-Blog-880x461.png 880w, https://blogcms.23andme.com/wp-content/uploads/2020/09/DEI-Blog-1180x618.png 1180w, https://blogcms.23andme.com/wp-content/uploads/2020/09/DEI-Blog.png 1200w" sizes="auto, (max-width: 1024px) 100vw, 1024px" /></figure>
 
“I read an article from 60 Minutes on CBS News recently that shared what most healthcare professionals already know: there is a healthcare disparity gap for minorities compared to their white peers. There are many reasons for this gap, many of which are rooted in the by-products of systemic racism. However, Dr. David Williams, a professor and chair at Harvard’s T.H. Chan School of Public Health, has spent his career researching and sharing information on what the CDC now recognizes: racism itself can be a killer.
Dr. Williams classifies the various levels of mistreatment using an <a href="https://scholar.harvard.edu/davidrwilliams/node/32397">Everyday Discrimination Scale</a>, which includes nine elements designed to assess an individual’s daily experience of discrimination. The scale tries to gauge well-being by asking questions like: 
<ul>
<li style="font-weight: 400;" aria-level="1">How often are individuals treated with less courtesy than others? </li>
<li style="font-weight: 400;" aria-level="1">How often are individuals treated with less respect than others? </li>
<li style="font-weight: 400;" aria-level="1">How often do they receive worse service in restaurants or stores? </li>
<li style="font-weight: 400;" aria-level="1">And how often do people act as if they’re afraid of them?</li>
</ul>
Individuals with a high score tend to also have adverse health outcomes. A high score is associated with high blood pressure, diabetes, cardiovascular disease, and poor mental health.
Dr. Williams’s research also demonstrates that the health of Black Americans suffers whether they are rich or poor, well-educated or not. For example, Black women with college degrees are more likely to see their babies die as infants than white women who didn&#8217;t finish high school. Even when they are treated in the same healthcare settings, Black Americans receive worse care. 
While there is nothing new for me from this article, this has been my ancestors&#8217; journey. And I appreciate the research that supports what we know — racism is a killer. To improve the health and well-being of minorities, we have to spend an equal amount of energy on eliminating racism. 
As a company that leads with science and is focused on improving the health outcomes for everyone, this provides us with another angle to help close the healthcare gap. As we work to conduct research and develop therapeutic solutions, we should also focus equal time and resources to eradicating racism.” 

<h2>Predicting Protein Structures with Atomic Accuracy</h2>
<a href="https://investors.23andme.com/corporate-governance/leadership">Adam Auton</a>, Vice President, Human Genetics

 <figure class="wp-block-image size-large is-style-default"><img loading="lazy" decoding="async" width="400" height="266" src="https://blogcms.23andme.com/wp-content/uploads/2009/10/dnaoragami.jpg" alt="" class="wp-image-5013" srcset="https://blogcms.23andme.com/wp-content/uploads/2009/10/dnaoragami.jpg 400w, https://blogcms.23andme.com/wp-content/uploads/2009/10/dnaoragami-300x200.jpg 300w" sizes="auto, (max-width: 400px) 100vw, 400px" /></figure>
 
“The<a href="https://deepmind.com/blog/article/alphafold-a-solution-to-a-50-year-old-grand-challenge-in-biology"> AlphaFold publication</a> is likely the most impactful research of the year regarding our ability to accurately predict protein structure. 
Understanding protein structure is critical for understanding biological function; knowing how a protein folds allows us to understand its shape and the protein&#8217;s function following that shape. 
However, predicting protein structure from the DNA sequence has been challenging for decades. As a result, only a relatively small number of proteins have had their structures &#8220;solved&#8221; by experimental means. 
This year, the DeepMind team released their AlphaFold technology, which used Machine Learning techniques to make tremendous strides in improving protein structure predictions. This technology has now been used to make structure predictions for every protein in the human genome and really opens a door for understanding biology in a way that wasn&#8217;t possible before.

<h2>The Past – and Future – of mRNA</h2>
<a href="https://www.lemonaidhealth.com/meet-our-lemons">Paul Johnson</a>, CEO, Lemonaid, and Vice President, General Manager Consumer
“The Fast Company article, <a href="https://www.fastcompany.com/90664662/how-biontech-created-a-new-delta-focused-covid-vaccine-in-just-a-few-weeks">How BioNTech created a new delta-focused COVID vaccine in just a few weeks</a>, described how creating some vaccines has become almost as easy as updating software code using mRNA. That was unheard of until recently and is critical as we encounter future viral illnesses and variants. It also lets us re-imagine how we might retool existing vaccines.<img loading="lazy" decoding="async" class="alignright size-full wp-image-29419" src="https://blog-api.23andme.com/wp-content/uploads/2021/12/Vaccine.png" alt="" width="164" height="168" />
Much like software, it&#8217;s now possible for biology to be sequenced and programmed using a &#8220;platform technology&#8221; so that if you change a sequence of the code, it is stable enough that everything else remains the same.  What used to take years now takes weeks. Like many breakthroughs, this discovery of mRNA as a potential platform in care delivery was not an overnight success. It was a consequence of risk-taking, personal sacrifice, and resilience. 
This <a href="https://www.statnews.com/2020/11/10/the-story-of-mrna-how-a-once-dismissed-idea-became-a-leading-technology-in-the-covid-vaccine-race/">background article</a> written before the approval of the mRNA vaccine is equally inspiring. It details the bold vision of Hungarian-born scientist Katalin Karikó, who spent the 1990s getting rejected for her grants for mRNA. 
In 1995, she was demoted when her bosses thought the pursuit of mRNA was a dead end. Yet, she persisted, and the foundational science behind her work is the pillar to our mRNA vaccines today.” 

<h2>Polygenic Scores Enter the Mainstream</h2>
<a href="https://blog.23andme.com/articles/be-fascinated-for-womens-history-month/">Shirley Wu</a>, Director, Product Science

 <figure class="wp-block-image size-large is-style-default"><img loading="lazy" decoding="async" width="1024" height="155" src="https://blogcms.23andme.com/wp-content/uploads/2021/12/Polygenic-Risk-score-1024x155.png" alt="" class="wp-image-29420" srcset="https://blogcms.23andme.com/wp-content/uploads/2021/12/Polygenic-Risk-score-1024x155.png 1024w, https://blogcms.23andme.com/wp-content/uploads/2021/12/Polygenic-Risk-score-300x45.png 300w, https://blogcms.23andme.com/wp-content/uploads/2021/12/Polygenic-Risk-score-768x116.png 768w, https://blogcms.23andme.com/wp-content/uploads/2021/12/Polygenic-Risk-score-880x133.png 880w, https://blogcms.23andme.com/wp-content/uploads/2021/12/Polygenic-Risk-score.png 1026w" sizes="auto, (max-width: 1024px) 100vw, 1024px" /></figure>
 
“While there have been many compelling genetics stories related to the COVID-19 pandemic, one theme in genetics that I’ve found very interesting this year was the conversation around polygenic scores. 
Polygenic scores are statistical models that combine the effects of potentially thousands or millions of genetic factors, sometimes alongside other factors, to predict the likelihood of a disease or trait in an individual. These started to become part of the academic sphere about five to eight years ago, but this year it became clear that they’ve entered the mainstream. 
Biotech and pharmaceutical companies are leveraging them to improve drug development, healthcare systems are beginning to apply polygenic scores to patient populations, and companies (including 23andMe) are offering them to consumers and healthcare providers. 
With that comes all the <a href="https://genomemedicine.biomedcentral.com/articles/10.1186/s13073-021-00829-7" target="_blank" rel="noopener" data-saferedirecturl="https://www.google.com/url?q=https://genomemedicine.biomedcentral.com/articles/10.1186/s13073-021-00829-7&amp;source=gmail&amp;ust=1641313460594000&amp;usg=AOvVaw09nnlrAHzEpbAqzEBbQVE3">challenges and debates</a> around ensuring validity, demonstrating utility, and ethical questions. Also, are models that predict traits like intelligence or neurodivergence <a href="https://www.newyorker.com/magazine/2021/09/13/can-progressives-be-convinced-that-genetics-matters" target="_blank" rel="noopener" data-saferedirecturl="https://www.google.com/url?q=https://www.newyorker.com/magazine/2021/09/13/can-progressives-be-convinced-that-genetics-matters&amp;source=gmail&amp;ust=1641313460594000&amp;usg=AOvVaw0TZiNtUsOxzKUYVlMWq8HN">appropriate</a>? And how do we address health disparities, given that most of the data underlying these models are from samples of European descent?
A common thread that ties this discussion to what we do at 23andMe is figuring out how to broaden access to the benefits of the genome in a responsible, science-driven way. I’ll follow closely where this conversation goes in the next year and beyond!”

23andMe Blog

23andMe Blog Team

New Genetic Findings on Melanoma

The opioid crisis presents a public health emergency without clear solutions. One key to unraveling the problem is understanding not just the causes of addiction, but understanding the steps taken leading people toward addiction.
A new genetic study by a team of scientists at UC San Diego School of Medicine proposed a cost-effective approach for studying the genetic basis of opioid addiction — termed “opioid use disorder” in the study — in large population-based cohorts instead of clinical cohorts.
Published in the journal<a href="https://t.umblr.com/redirect?z=https%3A%2F%2Fwww.nature.com%2Farticles%2Fs41380-021-01335-3&amp;t=OTRiN2RkZjZkNzY4MmI1NTliNDE0N2JmZDRiOTUxOTE0YTNhNTZhYSwwUFJVaEliQw%3D%3D&amp;b=t%3AP0Uz1DUMutRMdlhoe0mDtg&amp;p=https%3A%2F%2Fucsdhealthsciences.tumblr.com%2Fpost%2F666758608951934976%2Fgenetic-signals-linked-to-problematic-opioid-use&amp;m=0&amp;ts=1635872583"> Molecular Psychiatry</a>, the study was led by Sandra Sanchez Roige, Ph.D., and Abraham Palmer, Ph.D.
Using data from more than 132,000 23andMe customers who consented to participate in research, the study is important because it focused on the opioid misuse that can lead to opioid use disorder. In past decades opioid addiction started with heroin, but in this new era more than 80 percent of opioid addiction begins with the use of a prescription pain reliever, according to the study.
So, for this study, the researchers performed a genome-wide association study looking simply at participants reporting that&nbsp; they had ‘ever taken prescription painkillers not as prescribed.’ Essentially the researchers identified those in the first step toward from use to misuse of opioids, as a way to study the genetic underpinnings of the condition.
“Our results show that this single question captured a genetic signal that is correlated with signals from well-characterized cohorts that have been clinically diagnosed with (opioid use disorder.)”
The UC San Diego team discovered novel genomic regions that influenced using opiate drugs not as prescribed. They also identified strong genetic correlations with other substance use traits, including opioid use disorder.
Read the full study in<a href="https://t.umblr.com/redirect?z=https%3A%2F%2Fwww.nature.com%2Farticles%2Fs41380-021-01335-3&amp;t=OTRiN2RkZjZkNzY4MmI1NTliNDE0N2JmZDRiOTUxOTE0YTNhNTZhYSwwUFJVaEliQw%3D%3D&amp;b=t%3AP0Uz1DUMutRMdlhoe0mDtg&amp;p=https%3A%2F%2Fucsdhealthsciences.tumblr.com%2Fpost%2F666758608951934976%2Fgenetic-signals-linked-to-problematic-opioid-use&amp;m=0&amp;ts=1635872583"> Molecular Psychiatry</a>.

Understanding Opioid Use Disorder

A large new study by a team of international researchers has identified shared genetic associations between irritable bowel syndrome and mental health conditions such as anxiety and depression.
The study, published in the journal <a href="https://www.nature.com/articles/s41588-021-00950-8">Nature</a>, used data from more than 50,000 people with irritable bowel syndrome (IBS) and found that its symptoms may be caused by the same biological processes that trigger anxiety, depression, and insomnia.
<h6>Shared Genetic Origin</h6>
While the <a href="https://www.cam.ac.uk/research/news/large-scale-genetic-study-reveals-new-clues-for-the-shared-origins-of-irritable-bowel-syndrome-and">study</a> highlights the interconnections between the brain and digestive health, the researchers said that the findings don’t mean that anxiety or mood disorders cause IBS, or that IBS causes <a href="http://35.88.189.111/articles/new-23andme-report-on-anxiety">anxiety</a> and mood disorders. Rather, that certain genes are involved in the progression of both conditions.
“Although IBS occurs more frequently in those who are prone to anxiety, we don’t believe that one causes the other,” said<a href="http://www.med.cam.ac.uk/parkes/"> Professor Miles Parkes</a> of the University of Cambridge, who was a co-senior investigator and consulting gastroenterologist on this research. “Our study shows these conditions have shared genetic origins, with the affected genes possibly leading to physical changes in brain or nerve cells that in turn cause symptoms in the brain and symptoms in the gut.”
Past studies have shown that anxiety and depression often go hand-in-hand with IBS, but this study showed that these associations are because of actual shared genetic processes and not because someone may become depressed or anxious because of having IBS.
<h6>Common Conditions</h6>
IBS and anxiety are both quite common. In the U.S. estimates are that about<a href="https://www.nimh.nih.gov/health/statistics/any-anxiety-disorder"> 20 percent of adults</a> experience an anxiety disorder, meaning their anxiety has caused mild to severe impairment of their day-to-day lives. It is estimated that<a href="https://www.nature.com/articles/s41575-020-0286-8?proof=t#:~:text=Introduction-,Irritable%20bowel%20syndrome%20(IBS)%20is%20one%20of%20the%20most%20common,in%2010%20people%20globally1."> worldwide about one in 10 people</a> are affected by IBS. Symptoms of IBS include abdominal pain, bloating or bowel dysfunction significant enough to interfere with day-to-day activity. The causes of IBS are not well understood. But it tends to run in families and is more common in people who are prone to anxiety and other mood disorders.
For this study, the team of researchers from 40 different institutions identified different loci in six genes associated with IBS. Loci in four of those genes were also associated with mood and anxiety disorders. The researchers first used data from both the UK Biobank and the<a href="http://www.bionut.ki.se/groups/mda/bellygenes/index.html"> Bellygenes Initiative</a> — a worldwide study looking at genetic links to IBS. All the data came primarily from people of European ancestry, and the researchers used data from another 400,000 individuals who do not have IBS as a control group. The team then replicated their findings using de-identified data from 23andMe customers who consented to participate in research, which included more than 200,000 individuals with IBS and another 1.3 million who do not have the condition. The study also found a strong genome-wide correlation between the risk of IBS, and the risk for anxiety, neuroticism, and depression. Although IBS symptoms affect the gut and bowels, the genes associated with increased risk for IBS are not expressed there. Instead, they appear to have a clearer role in the brain, and possibly the network of nerves that serve the gut.
One of the paper’s lead authors,<a href="https://www.bdi.ox.ac.uk/Team/chris-eijsbouts"> Chris Eijsbouts</a>, of the University of Oxford, said the new research could aid in the development of new treatments in the future for these conditions.
&#8220;Even genetic changes that have only subtle effects on IBS can provide clues about pathways to target therapeutically,” Eiisbouts said. “Unlike the individual genetic changes themselves, drugs targeting the pathways they tell us about may have a considerable impact on the condition, as we know from other disease areas.&#8221;
Find the study in Nature <a href="https://www.nature.com/articles/s41588-021-00950-8">here</a>.

New Genetic Study Finds Links Between Gut Issues with Anxiety

Editor&#8217;s note: A previous version of this blog post had an error in the HLA table, which has been corrected in this version.
By Janie Shelton, Ph.D., and Daniella Coker, MPH*
As part of 23andMe’s ongoing study into COVID-19, our scientists have recently looked at how people <a href="https://blog.23andme.com/23andme-research/covid-19-vaccine-reactions/">react differently to different vaccines</a>, noting that those who previously had COVID-19, as well as women and younger people reacted the strongest to the vaccine.
Following up on that data, we also wanted to better understand whether genetics could help explain those differences and whether that could help us better understand the virus. We found that some variants in a complex of genes involved in immune response are associated with being more likely to have a strong reaction to the vaccine and some make it less likely.

<h6>Participating in COVID-19 Research</h6>
Before we go into details it’s important to note that this kind of study is possible because millions of individuals have already been vaccinated. Among them are a large number of 23andMe customers who have consented to participate in research. That has allowed our scientists to quickly explore 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>. We’ve also looked 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>. In this latest study, we looked at the factors associated with “reactogenicity”, or how noticeable a person’s response was to the vaccine. Some reported feeling nothing at all while others reported feeling very ill. This gave our scientists the data needed to study whether genetics could explain those differences.
To do that we conducted a genome-wide association study looking at these different responses to the vaccine between those who described feeling “Not at all sick” to those who felt “Extremely sick.”
<h6>Genetic Associations</h6>
We found a strong association between variations in the HLA genes — the human leukocyte antigen complex which is involved in regulating immune response. These genes encode for a number of proteins that make up the major-histocompatibility complex, which is on the frontline of your immune system&#8217;s infection recognition system. These results show that variations in the HLA complex are related to the degree to which one feels ill after vaccination.
First, it’s helpful to understand a bit about how vaccines work. These vaccines teach your immune system to recognize and respond to the virus that causes COVID-19. The mRNA vaccines (e.g. Pfizer/BioNTech &amp; Moderna) introduce genetic instructions to make a harmless protein that is unique to the virus. The other most common vaccine in circulation is the Johnson &amp; Johnson/Jansen vaccine, which uses a viral vector encoding the spike protein. In all three of these vaccines, your immune system develops a response to the spike protein of SARS-CoV-2, so your immune system can recognize the virus faster if you become exposed and eliminate it before you become severely ill.
<h6>Immune Response</h6>
Given how the vaccines work, why would we expect the HLA to be involved? The primary function of HLA molecules is to present foreign antigens on the cell surface in order to elicit an immune response. As such, the HLA plays a key role in presenting the proteins derived from the vaccine to the immune system.
But why do some people feel very sick from their COVID-19 vaccine, and others don’t feel sick at all?
Our findings suggest that prior history of COVID-19, younger age, female sex, and the type of HLA alleles you carry are strong predictors. Note that in the below table effect sizes below 1.0 decrease the likelihood of a reaction to the vaccine and the ones above 1.0 increase the likelihood (all reported effect sizes are statistically significant after correction for multiple tests).

 <figure class="wp-block-image size-large is-style-default"><img loading="lazy" decoding="async" width="1008" height="368" src="https://blogcms.23andme.com/wp-content/uploads/2021/12/HLA-Alleles-React.jpg" alt="" class="wp-image-29352" srcset="https://blogcms.23andme.com/wp-content/uploads/2021/12/HLA-Alleles-React.jpg 1008w, https://blogcms.23andme.com/wp-content/uploads/2021/12/HLA-Alleles-React-300x110.jpg 300w, https://blogcms.23andme.com/wp-content/uploads/2021/12/HLA-Alleles-React-768x280.jpg 768w, https://blogcms.23andme.com/wp-content/uploads/2021/12/HLA-Alleles-React-880x321.jpg 880w" sizes="auto, (max-width: 1008px) 100vw, 1008px" /></figure>
 
<h6>Long-haulers</h6>
Other studies have also found variation among populations for other alleles within the HLA that are associated with the severity of COVID-19. So for example, <a href="https://onlinelibrary.wiley.com/doi/full/10.1111/tan.14284">a recent study</a> by researchers at the Translational and Clinical Research Institute within Newcastle University found that an allele protective against severe COVID-19 symptoms in the HLA gene, at HLA-DRB1*04:01, was found at much higher frequency in people of Northwestern European ancestry. (Other studies have also found a genetic link to susceptibility to <a href="https://blog.23andme.com/articles/study-on-pneumonia">pneumonia</a>, also linked to genes associated with immune response.)
23andMe’s data on genetic associations related to different reactions to the vaccine offers other clues about the complexity of COVID-19. It is part of our on-going work to better understand the virus and the best approaches to fight it. Along with the workaround how genetic differences in immune response and blood type may play a role, our researchers are studying the long-term effects of the virus. We hope to look at so-called COVID-19 long-haulers to determine whether genetics can also explain why some individuals suffer health effects from the virus for weeks, months, and longer.
For more, you can go to our COVID-19 Information Center <a href="https://you.23andme.com/covid19-study/">here</a>.
<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

Janie Shelton

The Genetics of Reactions to COVID-19 Vaccines

We’re excited to share our refreshed <a href="https://www.23andme.com/about/consent/">Research Consent document</a> that governs how 23andMe conducts Research. Although we have not changed our research program or how we use participants&#8217; data, we reorganized the content of the Research Consent and greatly simplified the language. We made these updates for two reasons:
<h6>To be in compliance with updated research regulations: <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>
Our revisions align with updates to a federal regulation known as the Common Rule, which governs how human subjects research is conducted in the United States. The updated Common Rule aims to make consents more clear and easier to read, and to better help people make decisions about research participation. Our revised Research Consent is in compliance with the current version of the Common Rule.
<h6>To respond to customer feedback:</h6>
We recently asked our customers for feedback on our Research Consent. Based on their feedback we made the following changes:
<ol>
<li aria-level="1">We shortened the Key Information Summary at the top of the document.</li>
<li aria-level="1">We highlighted topics most important to our customers in the Key Information Summary&nbsp;</li>
<li aria-level="1">We simplified the language throughout the Research Consent.&nbsp;</li>
<li aria-level="1">We added detailed information about how participant data contributes to 23andMe Research.</li>
</ol>
If you look at the new consent, you may notice the updated Key Information Summary, the more concise and simple language, and the real-world examples of research discoveries made possible by participants who shared their information. We believe that the new version will enable our customers to more easily find information that may help them decide whether or not to participate in 23andMe Research.
We hope you see these changes as improvements and can find within the document the answers to your questions about 23andMe Research.
If you have questions about these revisions you can contact the 23andMe Research Team at <a href="mailto:hpa@23andMe.com">hpa@23andMe.com</a>.

Updates to Improve our Research Consent

Scientists with 23andMe and Google have collaborated to develop an imputation reference panel using 23andMe’s <a href="https://blog.23andme.com/23andme-research/african-american-sequencing-project/">African American Sequencing Project </a>to help expand diversity in genetic health research. This new reference panel enables researchers to more accurately identify associations between genetic variants and traits or health conditions within Black Americans and other non-European populations.
&#8220;This work will help address disparities in genetic research, as researchers outside of 23andMe will be able to use this data to inform their studies,&#8221; said Jared O&#8217;Connell, a 23andMe senior scientist and lead author for the paper. 
<h6>Expanding Analysis</h6>
All participating individuals were contacted and specifically consented to sharing their sequencing data via <a href="https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001798.v2.p2">dbGaP</a> with qualified researchers.
An imputation reference panel consists of genome-wide variation discovered through whole-genome sequencing in a set of individuals. Researchers often use such reference panels to perform genotype imputation. Unlike whole-genome sequencing, genotyping microarrays look at hundreds of thousands of sites that are known to vary between individuals, not the entire genome. Hence, there are hundreds of millions of such sites that are not assayed by microarrays. 
Genotype imputation is the process of inferring genotypes at many of these missing sites. Much like a code breaker filling in missing letters in a message, scientists — using algorithms and data from a whole-genome sequenced reference panel — can predict, or impute, the missing letters of genetic data. This allows large-scale genetic studies to expand the number of genetic variants that can be analyzed. But currently, most publicly available reference panels only include people of European ancestry, which limits their applicability to other populations.
<h6>A Reference Panel for Research</h6>
In this effort, described in <a href="https://www.nature.com/articles/s42003-021-02777-9">“A population-specific reference panel for improved genotype imputation in African Americans”</a> published this month, the teams built an imputation reference panel with high levels of African ancestry. It is the first peer-reviewed publication derived from 23andMe’s <a href="https://blog.23andme.com/23andme-research/african-american-sequencing-project/">African American Sequencing Project. </a> The panel includes genetic sequence data from more than 2,000 volunteers residing in the US, who identified as Black. With their consent, 23andMe created a reference dataset for research that consists of a de-identified reference panel and associated raw sequencing data. By including more individuals with non-European ancestry within the panel, imputation in non-Europeans is improved. For comparison, the commonly-used <a href="http://www.haplotype-reference-consortium.org/">Haplotype Reference Consortium</a> panel consists of 27,166 individuals which are predominantly of European descent. There is a subset of 2,001 individuals in that panel included from <a href="https://www.internationalgenome.org/">the 1000 Genomes Project</a>, and just 661 of these have substantial African ancestry.
&#8220;This biased reference panel composition generally leads to substantially poorer imputation quality for non-Europeans than for Europeans,&#8221; according to <a href="https://www.nature.com/articles/s42003-021-02777-9">the paper</a>. 
<h6>DeepVariant</h6>
Additionally, the team leveraged Google&#8217;s state-of-the-art variant caller, <a href="https://github.com/google/deepvariant">DeepVariant.</a> This allowed the researchers to further improve both the accuracy and richness of genetic variation in the reference panel. DeepVariant was compared with two versions of the popular GATK caller. It was shown to have a more accurate single sample calling performance as well as generate better performing imputation panels. Extensive comparisons of genotype refinement and phasing software were also conducted to establish a useful pipeline for creating imputation panels with DeepVariant. 
&#8220;The best practices for creating imputation panels we outline here are broadly applicable for improving imputation quality in non-European populations,&#8221; said senior author and Google staff software engineer Cory McLean.
This reference dataset was uploaded to the National Institute of Health&#8217;s dbGaP. It has already helped researchers studying conditions such as lymphoma, neurodegenerative disease, and cardiovascular disease. The reference dataset is also available to other qualified and vetted genetic scientists. It is meant to help expand research in Black Americans and other populations.
The team also published a blog post about the research <a href="https://healthcommunity.nature.com/posts/a-new-resource-for-african-american-genetics">here</a>.

Helping Expand Diversity in Genetic Health Research

In genetics, pedigrees are essential for many more reasons than you might think.
It is not just about creating family trees or seeing how family members are related. Pedigrees are also helpful for studying diseases and understanding broader questions about family structure and how people marry and migrate. They can also be used to discover facts about long-dead ancestors, such as their phenotypic traits and where they came from.
<h2>A New Method Called Bonsai</h2>
Researchers at 23andMe recently created a new method for inferring large human pedigrees. The American Journal of Human Genetics published this new method, dubbed Bonsai, which uses a new algorithm to build very large pedigrees. These new methods can quickly and efficiently assemble small pedigrees into a larger family tree that shows degrees of separation between individuals.
<div id="attachment_29249" style="width: 1034px" class="wp-caption aligncenter"><img loading="lazy" decoding="async" aria-describedby="caption-attachment-29249" class="wp-image-29249 size-large" src="http://35.88.189.111/wp-content/uploads/2021/10/F1.large_-1024x434.jpg" alt="An illustration of some of what goes into the Bonsai method for creating very large human pedigrees." width="1024" height="434" srcset="https://blogcms.23andme.com/wp-content/uploads/2021/10/F1.large_-1024x434.jpg 1024w, https://blogcms.23andme.com/wp-content/uploads/2021/10/F1.large_-300x127.jpg 300w, https://blogcms.23andme.com/wp-content/uploads/2021/10/F1.large_-768x325.jpg 768w, https://blogcms.23andme.com/wp-content/uploads/2021/10/F1.large_-880x373.jpg 880w, https://blogcms.23andme.com/wp-content/uploads/2021/10/F1.large_-1180x500.jpg 1180w, https://blogcms.23andme.com/wp-content/uploads/2021/10/F1.large_.jpg 1280w" sizes="auto, (max-width: 1024px) 100vw, 1024px" />An illustration of some of what goes into the Bonsai method for creating very large human pedigrees.</div>
These pedigrees can also help in studying the link between genetics and disease. Pedigrees can be helpful, especially when a disease is rare. In Genome-Wide Association Studies — a common method for discovering the genetic factors related to a common phenotype or disease — scientists must thin their sample to remove close relatives. Or they must leverage known relationships to increase the number of subjects that can be included, thus the statistical power for detecting associations. If full pedigrees are known, it opens the door for using a broader range of statistical methods. This, in turn, can be used to detect disease association and discover so-called de novo mutations that occurred for the first time in a family member.
<h2>Bridging Gaps</h2>
The ability to construct extensive pedigrees is also helpful for genealogy. In particular, the ability to use genetic data to infer pedigrees can help
<div id="attachment_29247" style="width: 228px" class="wp-caption alignright"><img loading="lazy" decoding="async" aria-describedby="caption-attachment-29247" class="wp-image-29247 size-medium" src="https://blog-api.23andme.com/wp-content/uploads/2021/10/Ethan-Jewett3385-218x300.jpg" alt="" width="218" height="300" srcset="https://blogcms.23andme.com/wp-content/uploads/2021/10/Ethan-Jewett3385-218x300.jpg 218w, https://blogcms.23andme.com/wp-content/uploads/2021/10/Ethan-Jewett3385-768x1056.jpg 768w, https://blogcms.23andme.com/wp-content/uploads/2021/10/Ethan-Jewett3385-745x1024.jpg 745w, https://blogcms.23andme.com/wp-content/uploads/2021/10/Ethan-Jewett3385-640x880.jpg 640w, https://blogcms.23andme.com/wp-content/uploads/2021/10/Ethan-Jewett3385-858x1180.jpg 858w, https://blogcms.23andme.com/wp-content/uploads/2021/10/Ethan-Jewett3385-scaled.jpg 1862w" sizes="auto, (max-width: 218px) 100vw, 218px" />Ethan Jewett, Ph.D., a 23andMe population geneticist.</div>
bridge gaps in historical records and help detect places where the records may be inaccurate. Using the reverse rules of Mendelian inheritance makes it possible to assign present-day alleles to the ancestors from whom they came, thus revealing the genotypes carried by long-dead ancestors. When these alleles are associated with phenotypes or ancestry from a particular population, it&#8217;s possible to make educated guesses about the physical traits of ancestors. One could use the same method to find out where they came from.
23andMe’s new Bonsai method improves existing methods for building extensive pedigrees and opens up other possibilities, said Ethan Jewett, Ph. D., a 23andMe population geneticist working on probabilistic methods and lead author of the paper.
“Big pedigrees make it possible to explore questions about family structure,&#8221; Ethan said. &#8220;For instance, how common a certain type of relationship is in a given population, like double cousins.”
<h2>Large Pedigrees</h2>
Pedigrees inferred from DNA allow researchers to examine other issues. They could help determine how often a self-reported pedigree agrees with an inferred pedigree. In other words, they can tell us how well people know their family trees. The paper found several instances of self-reported family trees with at least one misidentified relationship.
There are other larger population-level insights researchers can learn from these large pedigrees. For example, the method allows researchers to determine the ancestry composition of the average pedigree in the United States, traced back several generations. Another example of the process could help answer questions like how often people have kids with people outside of their cultural or ancestral group. This work can also help improve our understanding of the age distributions for different types of relationships, such as parent-child, or grandparent-grandchild, or first cousins. That ultimately can help in 23andMe’s ability to predict relationships. Understanding those relationships can also offer insights into human history and disease.
This new method improves the efficiency and accuracy of building large and complex human pedigrees.
You can read more about the method <a href="https://www.cell.com/ajhg/fulltext/S0002-9297(21)00349-9">here</a>.

A New Method for Creating Large Human Pedigrees

23andMe scientists recently shared some encouraging preliminary findings with participants in our Black Representation in Genomic Research study. The study is meant to help accelerate scientific discoveries and medical insights that directly benefit the Black community.
The scientists digging into the data believe these early findings offer encouraging signs that their work will indeed help alleviate some of the massive disparities in health and genetic research in non-European populations. The study itself is part of an on-going effort by 23andMe to improve diversity in research. That’s crucially important, according to speakers during the webinar.
“It’s knowledge that could help level the playing field,” said John Carpten, Ph.D., a Professor and Chair of Translational Genomics, as well as the Director of the Institute of Translational Genomics.
<h2>The Important of Diversity in Research</h2>
Professor Carpten was one of three outside scientists participating in the webinar. The other speakers included <a href="https://profiles.stanford.edu/carlos-bustamante">Carlos Bustamante</a>, Ph.D., a professor at Stanford University. He is an internationally recognized leader in applying data science and genomics technology to problems in medicine, agriculture, and biology. Also among the speakers was <a href="https://icahn.mssm.edu/profiles/eimear-kenny">Eimear Kenney</a>, Ph.D., the founding Director of the Institute for Genomic Health and Associate Professor of Medicine and Genetics at Mount Sinai. She leads research at the interface of genomics, medicine, and computer science.
They each noted the importance of diversifying genetic research and participation to ensure that all people, no matter their ethnicity, benefit from medical and scientific breakthroughs.
<h2>A Lack of Representation in Resarch</h2>
There is still much to be done, however. One <a href="https://www.cell.com/cell/fulltext/S0092-8674(19)30231-4">estimate in 2018</a> found that 78 percent of genome-wide association studies contained data from people only of European descent. The lack of data from non-Europeans, especially those of African descent, leads to less effective treatments for members of the Black community. Over the last decade, 23andMe has taken steps to improve the diversity of our research. Whether through the<a href="https://www.23andme.com/roots/"> Roots into the Future Project</a>, the<a href="https://www.23andme.com/africa-project/"> African Genetics Project</a>, or<a href="https://blog.23andme.com/23andme-research/african-american-sequencing-project/"> African American Sequencing Project,</a> each project was meant to enhance the diversity in our research and our product.
23andMe’s Black Representation in Genomic Research is another step in that journey. It will offer a way to include underrepresented populations in crucial medical research so that they too can benefit from those breakthroughs.
<h2>The Black Representation in Genomic Research Study</h2>
As part of this study, 23andMe recruited more than 1,000 people with African ancestry who consented to participate in research. The median age of participants is 37. Most of those who participated were in New York, California, Texas, Georgia and Florida. In addition about 69 percent were women, and most of those who participated had West African ancestry. The study involved using whole-genome and RNA sequencing data to study gene expression in people with African ancestry. This kind of “functional data” is crucial for understanding the significance of genetic variants identified through genome-wide association studies that, in turn, can help in developing treatments for diseases.
Unfortunately, because of the lack of representation in current research, there is not much gene expression reference data for people of African ancestry. The Black Representation in Genomic Research study is an effort to change that. And ensure that the Black community can benefit from scientific discoveries and drug development. The anonymized data from this study will help not just 23andMe researchers but also other academic researchers through the National Institutes of Health’s dbGaP.
<h2>Sharing Preliminary Study Findings</h2>
The webinar held earlier this Fall was an effort to share with those participating in the research some of what our scientists have learned so far and to answer their questions.
<div id="attachment_29289" style="width: 1034px" class="wp-caption aligncenter"><img loading="lazy" decoding="async" aria-describedby="caption-attachment-29289" class="wp-image-29289 size-large" src="https://blog-api.23andme.com/wp-content/uploads/2021/10/BRGR-ASHG-Poster-Kipper-1024x576.jpg" alt="" 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 poster presented during  <a href="https://www.ashg.org/meetings/2021meeting/">American Society of Human Genetics,</a> showing some of the preliminary data from the BRGR study.</div>
23andMe computational biologist Kipper Fletez-Brant, Ph.D., one of the 23andMe scientists working on the study, also spoke during the webinar.
23andMe now has one of the largest genetic research datasets for people of African ancestry in the world. While we still need to improve representation in our research data, that large dataset allows 23andMe to bring new insight into research specific to people of African ancestry.
The effort is important for a number of reasons, and Kipper gave the example of how different conditions — certain cancers, diabetes, and asthma, for example — impact people of African ancestry differently. Some of those differences are due to environmental and social differences but genetics may also play a role, Kipper said. In addition, certain medications may also be more or less effective in people of African ancestry because of those differences. He said that studies like the Black Representation in Genomic Research that look at functional data will help better understand those differences.
A description of the BRGR study will also be presented at the upcoming annual meeting of the <a href="https://www.ashg.org/meetings/2021meeting/">American Society of Human Genetics</a>.

Research — Page 13

Top genetic and science stories of 2021