Among the talks and presentations at the <a href="https://www.ashg.org/meetings/2023meeting/">annual meeting of the American Society of Human Genetics</a> during the first week of November in Washington D.C. will be two poster presentations by 23andMe scientists on new genetic findings around COVID and long COVID.



The poster presentations are part of a collection of presentations, panel discussions, and talks by scientists from 23andMe at this year’s conference.&nbsp;



<figure class="wp-block-image size-large"><img loading="lazy" decoding="async" width="1024" height="477" src="http://35.88.189.111/wp-content/uploads/2021/12/COVID-Image-1024x477.png" alt="A logo for 23andMe's COVID-19 Research Study" 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>



23andMe’s Vice President of Genomic Health, Noura Abul-Husn, M.D. Ph.D. will be on a panel focused on returning genetic results to consumers. 23andMe senior research project manager Anjali Shashtri, Ph. D., will talk on a separate panel about 23andMe’s efforts in building trust and research participation within underrepresented populations.



ASHG expects more than 8,000 researchers and clinicians at this year’s meeting, where they&#8217;ll share emerging discoveries and new genetic research.&nbsp;



“Human genetics is transforming science and health at a rapid pace, and ASHG’s 75th anniversary Annual Meeting provides both a milestone in the history of human genetics and genomics and a moment to look to a future in which genetics research improves the health and wellbeing of people everywhere,” said ASHG President Brendan Lee, MD, PhD. “Thousands of our members from across the globe will join to network, share discoveries, and explore new ways to apply genetics knowledge.”



<h6 class="wp-block-heading" id="h-23andme-covid-research">23andMe COVID Research</h6>



The two COVID presentations highlight include data on novel genetic variants associated with long COVID and other variants associated with COVID and having the symptom of diarrhea. Other studies have shown that having diarrhea may prolong the time it takes to clear the virus from their bodies, increasing the chances of more severe symptoms.



The two studies are part of ongoing COVID research 23andMe began soon after the pandemic emerged in 2020.&nbsp;



The work has revealed new insights on <a href="https://blog.23andme.com/23andme-research/23andme-covid-study-published/">the role blood type plays</a> in severity and susceptibility to the virus, as well as insights into the genetics that influence <a href="https://blog.23andme.com/23andme-research/reaction-to-covid-vaccine/">different reactions</a> to COVID-19 vaccines. In early 2022, 23andMe published a study in<a href="https://www.nature.com/articles/s41588-021-00986-w"> Nature Genetics</a> that identified genetic variants associated with the loss of smell or taste due to COVID-19. That paper offers more detail on the study, which identified variants near two olfactory genes — UGT2A1 and UGT2A2.



<h6 class="wp-block-heading" id="h-long-covid">Long COVID</h6>



The work presented this year at ASHG includes data on novel variants associated with long COVID. The variants are in genes within the human leukocyte antigen (HLA) complex related to immune response. Studies previously revealed an association of one of the variants with COPD, another with an allergic response, and a third with a response to viral infection.&nbsp;



The new data may help as researchers are still trying to determine why some people with COVID develop long COVID. Estimates suggest that between 12 -to- 16 percent of people with COVID will develop long COVID. The risk of long COVID is much higher among COVID patients with symptoms that are serious enough to require hospitalization.&nbsp;&nbsp;



One of the largest of its kind, this study included data from 140,000 23andMe customers who consented to participate in research, 41,000 of whom had long COVID.&nbsp;



The study also confirmed some previous findings and found novel genetic variants associated with long COVID. Among those were that females were likelier to develop long COVID than males. Individuals with long COVID are also more likely to have had depression, smoked cigarettes, or have had high blood pressure than those who do not develop long COVID. In addition, the researchers found genetic correlations between long COVID and conditions such as chronic fatigue, fibromyalgia, chronic pain, and depression.



<h6 class="wp-block-heading" id="h-covid-and-diarrhea">COVID and Diarrhea</h6>



23andMe’s second COVID-related presentation at the ASHG conference includes new genetic findings about individuals with COVID who also experience diarrhea. The study included data from about 140,000 people with COVID who also consented to participate in 23andMe’s research; of that total, about 80,000 reported having diarrhea as a symptom of COVID.



The researchers found several novel genetic variants associated with diarrhea and COVID-19. The strongest association was in the gene CYP7A1, associated with lipid function and cholesterol levels. Researchers also found an association with a variant in the gene CCR9, which was previously associated with susceptibility to COVID. Another variant associated with diarrhea among those with COVID was a variant in the gene GCKR, which is associated with fasting plasma glucose and chronic kidney disease.



<h6 class="wp-block-heading" id="h-23andme-other-research-presentations">23andMe Other Research Presentations</h6>



The conference will include a broad range of research across the field of genomics.&nbsp;



Along with the presentations on COVID and long COVID and panel discussions, 23andMe scientists will also be presenting some of our latest research on using polygenic risk scores to make earlier diagnoses of diabetes, evaluating the contributions of both rare and common variants in disease risk, and details from the study on the genetic legacy of African Americans from the Catoctin Furnace.&nbsp;



<hr class="wp-block-separator has-alpha-channel-opacity"/>



<figure class="wp-block-image aligncenter size-full"><img loading="lazy" decoding="async" width="174" height="87" src="http://35.88.189.111/wp-content/uploads/2023/10/ASHG-logo-75anniversary.png" alt="" class="wp-image-32283"/></figure>



<h6 class="wp-block-heading" id="h-23andme-s-presentations-amp-panels">23andMe&#8217;s Presentations &amp; Panels</h6>



<ul class="wp-block-list">
<li>Noura Abul-Husn, M.D. Ph.D., 23andMe Vice President of Genomic Health </li>



<li>Presenter: “Returning genomic results to consumers: The DTC approach”</li>



<li>Sat, Nov 4 8:50 &#8211; 9:05 am (ET) </li>



<li>Conv Ctr/Ballroom C/Level 3 </li>



<li>Presenter 04</li>
</ul>



<ul class="wp-block-list">
<li>Noura Abul-Husn, M.D. Ph.D., 23andMe Vice President of Genomic Health </li>



<li>Panelist: “Advancing Global Data Sharing and Complex Considerations” </li>



<li>Fri, Nov 3 3:00 &#8211; 4:15 pm (ET) </li>



<li>Conv Ctr/Room 152AB/Level 1</li>
</ul>



<ul class="wp-block-list">
<li>Anjali Shastri, Ph.D., 23andMe Senior Research Project Manager</li>



<li>Presenter: “Lessons learned in building trust and engaging underrepresented groups in direct-to-consumer genetic testing” </li>



<li>Sat, Nov 4 1:45 &#8211; 2:00 pm (ET) </li>



<li>Conv Ctr/Room 202A/Level 2</li>



<li>Presenter 06</li>
</ul>



<ul class="wp-block-list">
<li>Amy Sturm, Ph.D., 23andMe Director, Population Health Genomics</li>



<li>Session Co-Moderator “Harnessing return of value: Progress in returning genomic results to individuals in diverse, large-scale programs” </li>



<li>Sat, Nov 4 8:30 &#8211; 10:00 am (ET) </li>



<li>Conv Ctr/Ballroom C/Level 3 </li>



<li>Session 92</li>
</ul>



<h6 class="wp-block-heading" id="h-posters">Posters</h6>



<ul class="wp-block-list">
<li>Stella Aslibekyan, PhD, 23andMe Principal Scientist, Genetic Epidemiology </li>



<li>Poster: “Multi-ancestry analysis of COVID-19+ diarrhea reveals genetic associations with lipid function: a 23andMe Research Study” </li>



<li>Thu, Nov 2 3:00 &#8211; 5:00 pm (ET) </li>



<li>Board number 4160 </li>



<li>Presenter 054</li>
</ul>



<ul class="wp-block-list">
<li>Ninad S. Chaudhary, PhD,&nbsp; 23andMe Postdoctoral Fellow, Genetic Epidemiology </li>



<li>Poster: “Genetic architecture of Long COVID indicates associations with immune function, and shared etiology with chronic conditions in European population” </li>



<li>Thu, Nov 02 3:00pm &#8211; 5:00pm (ET) </li>



<li>Board number 1666 </li>



<li>Presenter 121</li>
</ul>



<ul class="wp-block-list">
<li>Zachary Fuller, PhD, 23andMe Scientist II, Statistical Geneticist </li>



<li>Poster: “Evaluating the contributions of rare and common variants in disease risk” </li>



<li>Fri, Nov 3; 3:00-5:00 pm ET </li>



<li>Board number 4137 </li>



<li>Presenter 47</li>
</ul>



<ul class="wp-block-list">
<li>Chris Germain, PhD, 23andMe Scientist I, Statistical Geneticist &amp; Machine Learning&nbsp;</li>



<li>Poster: “Polygenic risk and early diagnosis of diabetes” </li>



<li>Fri, Nov 3; 3:00-5:00 pm ET </li>



<li>Board number 4323 </li>



<li>Presenter 109</li>
</ul>



<ul class="wp-block-list">
<li>Éadaoin Harney, PhD, 23andMe Scientist I, Population Genetics R&amp;D&nbsp;</li>



<li>Poster: “The genetic legacy of African Americans from Catoctin Furnace”</li>



<li>Fri, Nov 3; 3:00-5:00 pm ET</li>



<li>Board number 3122</li>



<li>Presenter 122</li>
</ul>



<ul class="wp-block-list">
<li>Sarah Laskey, PhD, 23andMe Senior Scientist, Health R&amp;D&nbsp;</li>



<li>Poster: “Absolute and relative contextualization of polygenic scores in genetically diverse and admixed populations” </li>



<li>Fri, Nov 3; 3:00-5:00 pm ET </li>



<li>Board number 4338 </li>



<li>Presenter 114</li>
</ul>



<ul class="wp-block-list">
<li>Yanyu Liang, PhD, 23andMe Scientist I, Statistical Geneticist&nbsp;</li>



<li>Poster: “Credible set is sensitive to imputation quality and missing variants”</li>



<li>Fri, Nov 3; 3:00-5:00 pm ET</li>



<li>Board number 4107</li>



<li>Presenter 037</li>
</ul>



<ul class="wp-block-list">
<li>Shubham Saini, PhD, 23andMe Scientist I, Statistical Geneticist&nbsp; </li>



<li>Poster: “Population Scale Analysis of Copy Number Variation in 23andMe Research Cohort” </li>



<li>Fri, Nov 3; 3:00-5:00 pm ET </li>



<li>Board number 4326 </li>



<li>Presenter 110</li>
</ul>



<ul class="wp-block-list">
<li>Jingchunzi Shi, PhD, 23andMe Senior Scientist I, Genomics R&amp;D </li>



<li>Poster: “Evaluating genetically-predicted causal effects of lipoprotein(a) in human diseases: a phenome-wide Mendelian randomization study”</li>



<li>Fri, Nov 3; 3:00-5:00 pm ET</li>



<li>Board number 4136</li>



<li>Presenter 046</li>
</ul>



<ul class="wp-block-list">
<li>Wei Wang, PhD, 23andMe Senior Scientist I, Statistical Genetics</li>



<li>Poster: “A polygenic risk score of postoperative nausea and vomiting improves risk prediction and shows genetic correlation with CNS conditions including vertigo and motion sickness”</li>



<li>Fri, Nov 3; 3:00-5:00 pm ET</li>



<li>Board number 4209</li>



<li>Presenter 010</li>
</ul>



<ul class="wp-block-list">
<li>Amy Williams, PhD, 23andMe Senior Scientist II, Product R&amp;D </li>



<li>Poster: “Reconstructing parent genotypes at direct testing-level accuracy using siblings and other relatives.” </li>



<li>Thurs, Nov 2; 3:00-5:00 pm ET </li>



<li>Board number 3106 </li>



<li>Presenter 106</li>
</ul>



You can find out more about this year’s ASHG meeting <a href="https://www.ashg.org/meetings/2023meeting/">here</a>.

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

23andMe Blog

23andMe Blog Team

23andMe to Present New COVID Data at ASHG Conference

<h2>Our Alcoholism &amp; Genetics Study</h2>
Editor&#8217;s note: This article has been edited since it was first published in 2018. 
Building off of work done in 2017, a team of researchers led by scientists at the University of California, San Diego School of Medicine has identified new genetic variants associated with alcohol dependence in what is the largest genetic study of alcoholism ever done.
The <a href="https://ajp.psychiatryonline.org/doi/full/10.1176/appi.ajp.2018.18040369">study</a>, published in the <a href="https://ajp.psychiatryonline.org/action/captchaChallenge?redirectUri=%2F">American Journal of Psychiatry,</a> identified more than a dozen variants associated with &#8220;alcohol use disorder,&#8221; many of them identified for the first time.
The top hits were near genes that play a role in alcohol metabolism. While there is overlap between alcohol use disorder and alcohol consumption, the researchers did further analysis and found a “distinct genetic architecture” differentiating alcohol abuse from alcohol consumption. And these distinctions will be important for identifying the genetics of addiction, the researchers said.
<h2>What is Alcohol Use Disorder?</h2>
Alcohol use disorder, more commonly known as alcoholism, is characterized by an inability to control ones drinking because of a physical or emotional dependence of alcohol. Simply put it is an addiction to alcohol.
Researchers in this study found an overlapping association between alcohol abuse and psychiatric conditions such as depression, attention-deficit disorder, and schizophrenia. There was also overlap with other substance abuse issues including smoking, cannabis use and “increased consumption of multiple drug types.”
“We have shown that genetic risk for problematic alcohol drinking overlaps with psychopathology, including increased genetic risk for major depression, schizophrenia, and attention-deficit/hyperactivity disorder,” said co-author of the study Sandra Sanchez Roige, Ph.D., at, of UC San Diego School of Medicine&#8217;s Department of Psychiatry.
<h2>The Genetics of Alcoholism</h2>
The researchers used a questionnaire completed by participants to differentiate problem drinking from casual alcohol consumption, an important distinction in this study. Researchers were able to create a score for alcohol use, relying on an Alcohol Use Disorder Identification Test (AUDIT) that measures a broad spectrum of alcohol consumption. This in turn allowed the researchers to distinguish between casual drinking, alcohol abuse, and alcohol addiction, and identify that high scores were genetically correlated with a clinical diagnosis of alcohol dependence. The study also found that in contrast occasional drinking is associated with lower rates of depression, longer time in school, and lower rates of obesity.
“In fact, using this questionnaire in a population not ascertained for alcohol use disorders we have been able to achieve the largest sample size even obtained in the field of alcohol use disorders,” said Sanchez Roige.
<h2>Other Addictive Behavior</h2>
These findings are important for researchers because of similar overlap with other addictive behavior, said lead researcher<a href="https://profiles.ucsd.edu/abraham.palmer"> Prof. Abraham Palmer</a>.
<div id="attachment_25919" style="width: 1073px" class="wp-caption aligncenter"><img loading="lazy" decoding="async" aria-describedby="caption-attachment-25919" class="wp-image-25919 size-full" src="http://35.88.189.111/wp-content/uploads/2017/12/Abraham-Palmer-photo.jpg" alt="" width="1063" height="1600" srcset="https://blogcms.23andme.com/wp-content/uploads/2017/12/Abraham-Palmer-photo.jpg 1063w, https://blogcms.23andme.com/wp-content/uploads/2017/12/Abraham-Palmer-photo-199x300.jpg 199w, https://blogcms.23andme.com/wp-content/uploads/2017/12/Abraham-Palmer-photo-768x1156.jpg 768w, https://blogcms.23andme.com/wp-content/uploads/2017/12/Abraham-Palmer-photo-680x1024.jpg 680w, https://blogcms.23andme.com/wp-content/uploads/2017/12/Abraham-Palmer-photo-585x880.jpg 585w, https://blogcms.23andme.com/wp-content/uploads/2017/12/Abraham-Palmer-photo-784x1180.jpg 784w" sizes="auto, (max-width: 1063px) 100vw, 1063px" />Prof. Abraham Palmer</div>
“In terms of sample size, this is the largest sample ever used for a genetic study of alcoholism,” Palmer said. “Unlike prior efforts that focused on clinical diagnoses, which are relatively slow expensive on a per subject basis, our study used a 10-item screening questionnaire, that was originally developed by the World Health Organization. As a result, our collaboration with 23andme was done entirely via the Internet. That means it scales well; indeed, we plan to increase the sample size dramatically in the coming years.”
<h2>Health Costs of Alcohol Abuse</h2>
The study is also important because of the massive health and socio-economic impacts of substance abuse in general. Even just looking at alcohol alone there is a vast health cost, with more than 3.3 million people worldwide die each year from excessive alcohol use, according to the<a href="http://www.who.int/news-room/fact-sheets/detail/alcohol"> World Health Organization</a>. In the United States, the economic costs of alcohol abuse are estimated to be as high as $249 billion each year, according to the Centers for Disease Control.
While there are environmental and social factors that influence the risk for alcoholism, there is also a genetic component.
Scientists have learned through studies of identical and non-identical twins that alcohol use disorder is heritable, with genetic factors accounting for about half of the risk of alcohol dependence. But finding the genes that influence alcoholism has been challenging. Part of the challenge has been to gather a study that is large enough to detect a genetic signal, said Palmer.
<h2>Big Data</h2>
But the ability to tap into “big data” such as 23andMe’s research cohort as well as the UK Biobank, which Palmer and his team used for this study, has opened up new research opportunities for those studying behavioral traits — like addiction and substance abuse — as well as neuropsychiatric conditions and personality.
With data from more than 140,000 individuals, including aggregated data from 20,000 23andMe customers who consented to participate in research, this study was large enough to detect more than a dozen genetic variants associated with the alcohol use disorder.
“By studying different subsets,” according to the researchers. “We identify genetic factors that may be specific to problem drinking.”
The researchers believe that even larger studies may help to differentiate the genetics behind alcohol addiction.
“Our main focus is on further increasing sample size,” said Palmer. “Also, the present study focused on individuals of European ancestry, that’s because we had the largest sample in that group, however, we are very much interested in developing well-powered samples in other l populations.”
Beyond that, Palmer and his team want to develop a better understand of how the genes they’ve identified might influence these traits, but using animal and cellular models.
“Those biological insights are critical to potentially developing better strategies for prevention and treatment of alcoholism and related psychiatric disorders,” he said.

An image of a person drinking straight from a wine bottle

Is Alcoholism Genetic? Understanding the Genetics of Alcoholism

Editor&#8217;s note: This post has been edited slightly since it first appeared in 2020.



A <a href="https://www.nature.com/articles/s41562-020-00956-y">new study</a> that uncovered dozens of genetic associations for why some people are left-handed or ambidextrous offers potential new insight into the human brain&#8217;s structure and function. 



<figure class="wp-block-image alignright size-full is-resized"><img loading="lazy" decoding="async" width="724" height="483" src="http://35.88.189.111/wp-content/uploads/2022/09/GettyImages-1251025203.jpg" alt="" class="wp-image-30112" style="width:362px;height:242px" srcset="https://blogcms.23andme.com/wp-content/uploads/2022/09/GettyImages-1251025203.jpg 724w, https://blogcms.23andme.com/wp-content/uploads/2022/09/GettyImages-1251025203-300x200.jpg 300w" sizes="auto, (max-width: 724px) 100vw, 724px" /></figure>



In the largest study of its kind, researchers in Australia uncovered almost 50 genetic variants associated with being left-handed or ambidextrous. 



Using data from 1.7 million individuals, including more than 1.1 million 23andMe customers who consented to participate in research, scientists at the University of Queensland&#8217;s <a href="https://www.qimrberghofer.edu.au/">QIMR Berghofer Medical Research Institute</a>, found that many different genetic variants — each with a small effect — influence a person&#8217;s &#8220;handedness.&#8221;&nbsp; But the study also showed that while genetics plays an important role, environmental influences have a more significant impact on which hand a person favors. 



<h2 class="wp-block-heading" id="h-right-and-left-brain">Right and Left Brain</h2>



 Studying what researchers call &#8220;handedness&#8221; is significant because it offers insight into the brain&#8217;s lateralization. Lateralization refers to the tendency for different cognitive and neural functions — language, for instance — to be located on one side of the brain and not the other. In this study, the <a href="https://www.23andme.com/genetic-science/" target="_blank" rel="noopener">genetic associations</a> with left-handedness may also point to influences on the development of brain tissue that is important for generating new neurons and other functions that regulate brain development. 



&#8220;Although there is an enduring fascination with why some people are left or right-handed or both, understanding why some people are left-handed and others right-handed is also an important research question because handedness can influence brain structure and the way different functions are located within the brain,&#8221; said <a href="https://www.qimrberghofer.edu.au/people/sarah-medland/">Professor Sarah Medland</a>, co-senior author of the paper and head of QIMR Berghofer&#8217;s Psychiatric Genetics Group. 



The researchers also found genetic correlations with being left-handed and schizophrenia and having bipolar disorder. This raises questions about whether this is related to the influence on brain structure and function found in this research. 



<h2 class="wp-block-heading" id="h-large-study-size">Large Study Size</h2>



 For this study, the researchers combined data from many different research cohorts.&nbsp; The study included data not only from 23andMe customers, but also data from the UK Biobank, and 32 other researcher institutions from around the globe. 



All together it included data from about 1.5 million people who are right-handers, about 194,000 who are left-handers, and 37,000 who are ambidextrous. The study identified 41 genetic variants associated with being left-handed and seven associated with being ambidextrous. There is very little genetic correlation between being left-handed and being ambidextrous, according to the researchers. 



The study appears in the journal <a href="https://www.nature.com/articles/s41562-020-00956-y" target="_blank" rel="noopener noreferrer">Nature Human Behaviour</a>.

The Genetics of Being Left-Handed or Right-Handed

Researchers at Johns Hopkins Bloomberg School of Public Health, Harvard, the Broad Institute, the National Cancer Institute, and 23andMe have developed a method that significantly improves the performance of polygenic risk score models for people of non-European ancestry.



This new method holds promises that future clinical use of new polygenic models will be less likely to exacerbate health inequities.



<figure class="wp-block-image size-large"><img loading="lazy" decoding="async" width="1024" height="155" src="http://35.88.189.111/wp-content/uploads/2021/12/Polygenic-Risk-score-1024x155.png" alt="An illustration of polygenic risk score models
" 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>



<h2 class="wp-block-heading" id="h-what-are-polygenic-risk-scores">What Are Polygenic Risk Scores?</h2>



Over the last several years, these kinds of risk models, also known as <a href="https://blog.23andme.com/articles/nilanjan-chatterjee">polygenic risk scores, or PRS</a>, have begun to offer up meaningful risk information on many diseases like <a href="https://www.23andme.com/brca/">breast cancer</a>, <a href="https://blog.23andme.com/articles/screening-for-t2d">type 2 diabetes</a>, or <a href="https://www.23andme.com/topics/health-predispositions/coronary-artery-disease/">heart disease.</a> But the performance of these models — which rely on very large genome wide association studies and are based on hundreds or thousands or even many thousands of variants to calculate risk — perform poorly for non-Europeans. That’s in part because of the lack of genetic research that includes data from non-Europeans.



Outlined in a paper published in the journal <a href="https://www.nature.com/articles/s41588-023-01501-z">Nature Genetics,</a> this new method addresses that problem, improving both the performance and training and building speed of these risk models. 



<h2 class="wp-block-heading" id="h-how-is-the-new-polygenic-risk-model-changing-the-game">How Is the New Polygenic Risk Model Changing the Game?</h2>



Dubbed CT-SLEB, this new approach substantially improved the performance of polygenic risk models in diverse populations, especially among people with African ancestry. And these CT-SLEB models can be modeled much faster than other polygenic risk modeling methods.



“At 23andMe, we are committed to providing health value to everyone. With this collaborative study, we helped improve a method to make polygenic risk models perform better for underrepresented populations so that everyone can have a better understanding of their future health,” said Jianan Zhan, a senior scientist with 23andMe’s Product R&amp;D. “There’s great potential for using these models in clinical care too, but to make that a reality we need to make sure they work for people of all ancestries.”



<h2 class="wp-block-heading" id="h-how-the-prs-model-works">How the PRS Model Works</h2>



The scientists used three distinct steps in their approach. First, they used something they called “clumping and thresholding.” This allowed them to select risk variants relevant to different populations — European, African, East Asian, South Asian and Latino. Then, they used a statistical method called “Empirical-Bayes.” This statistical method uses the risk averages from the whole dataset to adjust the risk averages of each specific population. Finally, the team applied a third layer that involved a machine learning approach. Calling it “super learning,” this machine learning approach adjusts and improves the predictive accuracy of the polygenic risk model.



They then compared their model to nine other modeling methods across <a href="https://www.23andme.com/dna-ancestry/">five different ancestry groups</a>. They did this to test the predictive value for seven complex traits using data from more than 3.7 million 23andMe customers who consented to participate in research. These research participants were also of different ancestries. The 3.7 million includes more than 413,000 Latinos, 117,000 African Americans, 96,000 people of East Asian descent, and another 26,000 people of South Asian descent.  



It proved to be much faster, highly scalable and one of the most powerful methods for generating risk predictions in non-European populations, particularly among African Americans.



<h2 class="wp-block-heading" id="h-what-you-need-to-know-about-polygenic-risk-scores">What You Need to Know About Polygenic Risk Scores</h2>



While this new approach offers promise, the study authors noted some of the limitations. This new method substantially improved the performance of polygenic risk models in many settings, but there is still room to improve results for non-Europeans. 



In addition, the authors noted that the best approach for risk prediction might involve using multiple methods and combining the results. Even with best methods, the disparity in polygenic risk model performance may remain. That is unless there are larger sample sizes from understudied populations.



<a href="https://www.23andme.com/dna-reports-list/">23andMe offers more than 30 reports</a> based on polygenic risk models. The model is trained with a different method but includes some of the approaches outlined in this paper that were adjusted to account for the uniqueness of our database. You can learn more about our<a href="https://permalinks.23andme.com/pdf/23_21-PRSMethodology_May2020.pdf"> methods for creating these polygenic scores</a>.



With its large size and scale, 23andMe offers a unique opportunity to develop and improve upon these types of models with unmatched power.

Understanding Polygenic Risk Scores (PRS)

By Keaton Stagaman*



 It’s been noted at least since James Parkinson’s original essay describing the “shaking palsy” that some of the earliest symptoms of Parkinson’s disease (PD) involve the gut. So, 23andMe researchers, working in collaboration with The Michael J. Fox Foundation for Parkinson’s Research, are studying the microbiome of individuals with Parkinson’s disease to learn more about this “gut-brain axis” and what it can tell us about the disease.



This is the first time a single study with hundreds of people reporting Parkinson’s disease diagnosis who’ve consented to participate in this research have also included samples of both the gut and oral microbiomes.



The human body plays host to trillions of microbes—such as bacteria, archaea, and fungi— collectively called the microbiome. Over the past few decades, it has become abundantly clear to the scientific community that the microbiome plays an essential role in our development, physical health, and mental well-being. [1]&nbsp;



<figure class="wp-block-image size-full"><img loading="lazy" decoding="async" width="861" height="916" src="http://35.88.189.111/wp-content/uploads/2022/03/PD-Research.png" alt="" class="wp-image-29642" srcset="https://blogcms.23andme.com/wp-content/uploads/2022/03/PD-Research.png 861w, https://blogcms.23andme.com/wp-content/uploads/2022/03/PD-Research-282x300.png 282w, https://blogcms.23andme.com/wp-content/uploads/2022/03/PD-Research-768x817.png 768w, https://blogcms.23andme.com/wp-content/uploads/2022/03/PD-Research-827x880.png 827w" sizes="auto, (max-width: 861px) 100vw, 861px" /></figure>



This latter connection, between our minds and our microbes, particularly in our digestive tracts, is part of our “gut-brain axis.” Many neurological diseases like Parkinson’s disease that affect our brain and behavior — often begin with digestive tract issues as the first sign.&nbsp;



<h6 class="wp-block-heading" id="h-23andme-parkinson-s-research">23andMe Parkinson&#8217;s Research</h6>



23andMe has focused research efforts on Parkinson’s disease since 2009. Just under half of people diagnosed with Parkinson’s disease suffer from intestinal problems, such as constipation, and other more classical symptoms associated with the disease, such as tremors and slow movement.



While researchers have identified genes and environmental factors that may contribute to the risk, for those with Parkinson’s, the cause of their disease remains unknown. For several years, it has been thought that Parkinson’s might start in the gut. The hallmark of the disease is the buildup of misfolded protein (alpha-synuclein) deposits in nerve cells in the brain. One intriguing hypothesis is that this misfolding might start in the gastrointestinal tissue, and travel through the nervous system up to the brain. This, of course, opens the possibility that the gut microbiome might play a key role in the pathological onset of Parkinson’s disease.&nbsp;



<h6 class="wp-block-heading" id="h-the-microbiome">The Microbiome</h6>



Most studies of the microbiome in people with Parkinson’s disease have been in small populations and so far have led to more questions than answers. In order to investigate what role the microbiome might play in the development of Parkinson’s disease, 23andMe embarked on a large microbiome study in collaboration with The Michael J. Fox Foundation for Parkinson’s Research (MJFF). Back in 2021, we invited over 650 23andMe customers, about two thirds of whom had reported being diagnosed with PD, to participate in the study by providing stool and saliva microbiome samples. To our knowledge, this is the largest single study to test the relationships between both the oral and gut microbiomes and Parkinson’s disease, providing us with the statistical power to uncover potentially important associations.&nbsp;



Participants’ samples were sequenced using a high-tech method called shotgun metagenomics, which allows us to identify not only which microbes are present in the microbiome, but genes that these microbes harbor. This gives us information of “who” is in the microbiome, and “what” they’re capable of doing. Additionally, the participants completed a deep dive survey of microbiome-related questions, such as their age, dietary habits, and biological sex. Customers with Parkinson’s also provided detailed information about their symptoms, treatment, disease milestone, and daily functioning.



<h6 class="wp-block-heading" id="h-a-first">A First</h6>



The primary goal is to identify signatures of Parkinson’s disease in the microbiome. That is, are there specific microbes or specific microbial genes that are more likely to be present in people with Parkinson’s disease regardless of their age, biological sex, diet, or symptoms? Furthermore, we can identify microbes or microbial genes that are associated with specific Parkinson’s symptoms, how fast their disease has progressed, and how severe their symptoms are.



This is the first time a single study of this size has sampled both the gut and oral microbiomes. In doing so, we can identify links between the microbes in our mouth and gut and how this might contribute to Parkinson’s disease. As sampling saliva is much less cumbersome than sampling stool, spit-based microbiome sampling could provide us with a much easier way to test for the presence of microbial Parkinson’s disease indicators in the future.



The study included 427 customers with Parkinson’s and 226 customers without PD between the ages of 50 and 69. The customers with Parkinson’s were diagnosed, on average, at the age of 59 years old. They reported typical motor symptoms of PD including shaking tremor (67%), slowness of movement (47%), stiffness (40%). Around one-third also reported suffering from constipation. Our microbiome can differ substantially according to where we live. The samples collected in the study were collected across all 50 states in the US, which will make the findings widely geographically applicable.



With such a large cohort that has been willing to provide us with so much helpful information, this is a one-of-a-kind opportunity to study the relationship between the microbiome and Parkinson’s disease. More than 6 million people worldwide have Parkinson’s disease. For 23andMe, this is an opportunity to move the needle on what role gut microbes may play in Parkinson’s disease, which could open up new opportunities for customers with PD in the future. We are grateful to our 23andMe customers that were willing to provide their samples. We hope this will raise awareness that Parkinson’s disease goes beyond problems with movement, such as tremor and slow movement, and actually affects many other organ systems, like the gut.&nbsp;



<figure class="wp-block-image"><img decoding="async" src="https://lh5.googleusercontent.com/WmsPZ80pcYGHlMBpAga-YYvESjRvNWovWYD9aIheviUfEbvkX_IXnc8XEYUqfKK87pc_VBSFXbFS3mwKg3Rua2siq2iGiOFwJ30_yrn0z68oJGmQmhZqg4Nyp2nQ7G4fkBxrznOMgQHK0bbJL0ypgQ" alt=""/></figure>



<h6 class="wp-block-heading" id="h-future-microbiome-research">Future microbiome research</h6>



Beyond advancing Parkinson&#8217;s disease research, studying associations between the microbiome, human genetics, and disease could lead to greater insights into human health more broadly. 



Because of this, 23andMe has recently expanded its ability to study the microbiome by adding oral microbiome data from stored saliva samples to the data types that 23andMe researchers may analyze under our <a href="https://www.23andme.com/about/consent/">Research Consent Document</a>. By expanding the data types we can analyze to include the microbiome, we hope to power greater insights into human health and wellness. 



You can read more about these updates <a href="https://customercare.23andme.com/hc/en-us/articles/212195708-Research-Participation-and-Consent">here</a>.&nbsp;



<hr class="wp-block-separator has-alpha-channel-opacity"/>



<h6 class="wp-block-heading" id="h-citations">Citations</h6>



<ol class="wp-block-list">
<li>Cho, I., Blaser, M. The human microbiome: at the interface of health and disease. Nat Rev Genet 13, 260–270 (2012). <a href="https://doi.org/10.1038/nrg3182">https://doi.org/10.1038/nrg3182</a></li>
</ol>



*Keaton Stagaman is a postdoctoral fellow at 23andMe, whose position is funded by MJFF. He has authored numerous original research papers and reviews on the microbiomes of vertebrates, including zebrafish, mice, and humans. In his previous position as a postdoc at Oregon State University, he focused his research on the gut-brain axis. In particular, he studied what role the gut microbiome plays in how environmental toxicants and neurodegenerative diseases affect animal behavior.

Keaton Stagaman

Parkinson’s Disease and the Microbiome

A new study led by scientists who are part of the <a href="https://gp2.org/">Global Parkinson’s Genetic Program</a> has revealed important insights into Parkinson&#8217;s disease among people of African and mixed African ancestry, which has been largely unexplored until now.



<figure class="wp-block-image size-large"><img loading="lazy" decoding="async" width="1024" height="625" src="http://35.88.189.111/wp-content/uploads/2018/04/World-Map-1024x625.png" alt="A multi-colored image of world map, showing countries." class="wp-image-26132" srcset="https://blogcms.23andme.com/wp-content/uploads/2018/04/World-Map-1024x625.png 1024w, https://blogcms.23andme.com/wp-content/uploads/2018/04/World-Map-300x183.png 300w, https://blogcms.23andme.com/wp-content/uploads/2018/04/World-Map-768x469.png 768w, https://blogcms.23andme.com/wp-content/uploads/2018/04/World-Map-880x537.png 880w, https://blogcms.23andme.com/wp-content/uploads/2018/04/World-Map-1180x721.png 1180w, https://blogcms.23andme.com/wp-content/uploads/2018/04/World-Map.png 1600w" sizes="auto, (max-width: 1024px) 100vw, 1024px" /></figure>



<h2 class="wp-block-heading" id="h-global-parkinson-s-research">Global Parkinson&#8217;s Research</h2>



The Global Parkinson’s Genetic Program includes scientists working at dozens of institutions worldwide. This includes researchers at 23andMe as well the Nigerian Parkinson Disease Research Network, which includes universities and hospitals across Nigeria. In addition, the Global Parkinson’s Genetic Program includes scientists who are part of the Black and African American Connections to Parkinson’s Disease Study (BLAAC PD) study group. Scientists at the NIH, the <a href="https://www.michaeljfox.org/">Michael J. Fox Foundation</a>, the University of Lagos in Nigeria, and University College London as well as a half dozen hospitals and universities in the United States are part of this group.



&#8220;This is proof of principle for the Global Parkinson&#8217;s Genetics Program showing that increasing diversity and inclusivity in genetics studies can efficiently deliver novel insights,&#8221; said Dr. Sara Bandres Ciga, staff scientist at the NIH’s National Institute on Aging. 



<h2 class="wp-block-heading" id="h-african-research-institutions">African Research Institutions</h2>



Published in the journal <a href="https://www.sciencedirect.com/science/article/abs/pii/S1474442223002831?via%3Dihub">Lancet Neurology</a>, the research represents the first genome-wide association study of Parkinson&#8217;s disease in African and African admixed populations.&nbsp;



The Global Parkinson’s Genetic Program draws together data from existing research cohorts, then makes that data available for genetic research into Parkinson’s disease, making work like this possible.



“As researchers and clinicians, our shared responsibility is to make sure Parkinson’s science is representative of all communities around the world,” said Njideka Okubadejo, MD, Professor of Neurology at the University of Lagos, College of Medicine. “This GBA1 result is a step toward that future, where the research field is prioritizing, learning from, and treating all people with Parkinson’s disease.”&nbsp;&nbsp;&nbsp;



<h2 class="wp-block-heading" id="h-a-novel-variant-in-gba1">A Novel Variant in GBA1</h2>



 The research identified a novel signal at the GBA1 locus associated with a higher risk for Parkinson&#8217;s disease among people of African descent.



The top variant and potential functional variant is much rarer in people who do not have African ancestry. Although the gene GBA1 is known to be associated with Parkinson&#8217;s disease in other populations through coding variation, it is thought that this variant influences the expression of the gene and the production of glucocerebrosidase, an enzyme also known as GCase. A deficiency in this enzyme is characteristic of the rare genetic disorder Gaucher disease, which can lead to such things as an enlarged liver or spleen and bone abnormalities. In this case, it appears to impact how Parkinson&#8217;s develops in people with African ancestry. This single variant changes the expression of the gene GBA1, which results in decreasing levels of the GCase enzyme.



The study provides some critical insight into disease risk. This novel mechanism may hold promise for potential RNA-based therapeutic strategies, but researchers also believe the new study could inform future GBA1 clinical trials, improving patient stratification.&nbsp;



“Understanding the genetic landscape of diverse populations is not just a nod to inclusivity, but a scientific necessity,&#8221; said Mary B. Makarious, a predoctoral student working at the National Institute on Aging and a co-author of the study. &#8220;Unraveling these genetic factors, such as the variant in the GBA1 gene in people of African descent, offers us novel avenues to explore not just for disease prevention, but also for the development of targeted and potentially more effective treatments. Every discovery like this brings us closer to a more comprehensive understanding of this disease.&#8221;



According to researchers, African admixed populations offer unique opportunities for studying the genetics of both monogenic and complex diseases. This is because these populations contain the world&#8217;s largest portion of genetic variability.&nbsp;



Led by researchers at the Global Parkinson’s Genetic Program, work on the study included contributions from scientists at 23andMe and researchers across Africa. The work was supported by the Global Parkinson&#8217;s Genetics Program, funded by the Aligning Science Against Parkinson&#8217;s initiative, and implemented by The Michael J. Fox Foundation for Parkinson&#8217;s Research.&nbsp;



The study included data from just under 196,000 23andMe customers with African admixed ancestry who consented to participate in research.

Study of Parkinson’s Genetic Risk in African Populations

We don&#8217;t know their names, but a new historical DNA analysis by researchers at 23andMe, <a href="https://hms.harvard.edu/news/historical-dna-study-connects-living-people-enslaved" target="_blank" rel="noreferrer noopener">Harvard University</a>, and the Smithsonian Institution has revealed more about the enslaved and freed African Americans who labored at a Maryland iron furnace just after the founding of the United States. Along with insights into the lives of these forgotten people, the study leveraged 23andMe’s large research database to find connections between these people and more than 40,000 of their living relatives.&nbsp;



The stunning analysis published in the journal <a href="https://www.science.org/doi/full/10.1126/science.ade4995" target="_blank" rel="noreferrer noopener">Science reveals a hidden history</a>. (You can also find an open access <a href="http://35.88.189.111/wp-content/uploads/2023/08/Harney-etal-Catoctin-Science-AcceptedVersion_ForSharing-1.pdf" target="_blank" rel="noreferrer noopener">PDF of the paper here.</a>) Moreover, it provides a technical and ethical benchmark to inform future studies of similar, largely forgotten burial sites.&nbsp;



“Our study demonstrates the power of DNA to uncover important history about the lives of people whose stories are lost to time,” said lead author Éadaoin Harney, Ph.D., a 23andMe scientist on 23andMe’s Population Genetics R&amp;D team. “The study revealed more about these individuals, including identifying familial groups, discovering details of their ancestral origins in Africa, and connecting their history to people living today.”



<figure class="wp-block-gallery has-nested-images columns-default is-cropped wp-block-gallery-1 is-layout-flex wp-block-gallery-is-layout-flex">
<figure class="wp-block-image size-large"><img loading="lazy" decoding="async" width="731" height="1024" data-id="31969" src="http://35.88.189.111/wp-content/uploads/2023/07/Burial35_updated-731x1024.jpg" alt="A photo of a facial reconstruction of one of the individuals , a woman in her 30s, found at Cactoctin Furnace." class="wp-image-31969" srcset="https://blogcms.23andme.com/wp-content/uploads/2023/07/Burial35_updated-731x1024.jpg 731w, https://blogcms.23andme.com/wp-content/uploads/2023/07/Burial35_updated-214x300.jpg 214w, https://blogcms.23andme.com/wp-content/uploads/2023/07/Burial35_updated-768x1075.jpg 768w, https://blogcms.23andme.com/wp-content/uploads/2023/07/Burial35_updated-629x880.jpg 629w, https://blogcms.23andme.com/wp-content/uploads/2023/07/Burial35_updated-843x1180.jpg 843w, https://blogcms.23andme.com/wp-content/uploads/2023/07/Burial35_updated-scaled.jpg 1829w" sizes="auto, (max-width: 731px) 100vw, 731px" /><figcaption class="wp-element-caption">Courtesy of Catoctin Furnace Historical Society; forensic facial reconstruction by StudioEIS and artist Jiwoong Cheh in consultation with Smithsonian scientists; photography by James D. Tiller &amp; Miguel Montalvo, Smithsonian.</figcaption></figure>



<figure class="wp-block-image aligncenter size-large"><img loading="lazy" decoding="async" width="731" height="1024" data-id="31970" src="http://35.88.189.111/wp-content/uploads/2023/07/Burial15_updated-731x1024.jpg" alt="A photo of a facial reconstruction of one of the individuals , a teenage male, found at Cactoctin Furnace." class="wp-image-31970" srcset="https://blogcms.23andme.com/wp-content/uploads/2023/07/Burial15_updated-731x1024.jpg 731w, https://blogcms.23andme.com/wp-content/uploads/2023/07/Burial15_updated-214x300.jpg 214w, https://blogcms.23andme.com/wp-content/uploads/2023/07/Burial15_updated-768x1075.jpg 768w, https://blogcms.23andme.com/wp-content/uploads/2023/07/Burial15_updated-629x880.jpg 629w, https://blogcms.23andme.com/wp-content/uploads/2023/07/Burial15_updated-843x1180.jpg 843w, https://blogcms.23andme.com/wp-content/uploads/2023/07/Burial15_updated-scaled.jpg 1829w" sizes="auto, (max-width: 731px) 100vw, 731px" /><figcaption class="wp-element-caption">Courtesy of Catoctin Furnace Historical Society; forensic facial reconstruction by StudioEIS and artist Jiwoong Cheh in consultation with Smithsonian scientists; photography by James D. Tiller &amp; Miguel Montalvo, Smithsonian. </figcaption></figure>
</figure>



<h6 class="wp-block-heading">Connections to Early American Industrial Site</h6>



The researchers looked at the DNA from the remains of 27 individuals, many of them teenagers and children, excavated from a cemetery at the historic site of <a href="https://catoctinfurnace.org/ironworker/">Catoctin Furnace</a>. Among them are 15 related individuals clustered into five family groups, which were mostly made up of mothers, their children, and siblings. The remains of those related individuals were generally found buried near one another.&nbsp;



Their DNA indicates that these individuals had more ancestry connecting to a region now known as Senegal and Gambia and, more specifically, groups from that region, such as the Wolof and Mandinka, than do most modern-day African Americans. Many also had European ancestry, mainly from Britain and Ireland, likely due to the rape of enslaved African American women by their white enslavers and others in positions of power (who had primarily European ancestry). Further evidence of that exploitation was that much of the European ancestry was on the paternal side.&nbsp;



The highest concentration of the Catoctin individuals’ closest living genetic relatives are in Maryland, indicating that some surviving family members of those who labored at the forge remained in Maryland since the late 1700s or early 1800s.



<figure class="wp-block-image aligncenter size-large"><img loading="lazy" decoding="async" width="1024" height="541" src="http://35.88.189.111/wp-content/uploads/2023/07/Heat-Map-1024x541.png" alt="A heat map showing not just where living genetic relatives of the Catoctin Furnace are in the United States but also the ancestral contributions from Africa and Europe." class="wp-image-31963" srcset="https://blogcms.23andme.com/wp-content/uploads/2023/07/Heat-Map-1024x541.png 1024w, https://blogcms.23andme.com/wp-content/uploads/2023/07/Heat-Map-300x158.png 300w, https://blogcms.23andme.com/wp-content/uploads/2023/07/Heat-Map-768x406.png 768w, https://blogcms.23andme.com/wp-content/uploads/2023/07/Heat-Map-880x465.png 880w, https://blogcms.23andme.com/wp-content/uploads/2023/07/Heat-Map-1180x623.png 1180w, https://blogcms.23andme.com/wp-content/uploads/2023/07/Heat-Map.png 1522w" sizes="auto, (max-width: 1024px) 100vw, 1024px" /><figcaption class="wp-element-caption">Site of Catoctin Furnace in Maryland (star) and locations of deidentified study participants (colored dots). Darker dots indicate more participants related to those at the burial site. Image: Harney et al, Science</figcaption></figure>



<h6 class="wp-block-heading" id="h-reconnecting-to-lost-roots">Reconnecting to Lost Roots</h6>



<a href="https://www.harvardmagazine.com/2022/07/feature-ancient-dna">Harvard geneticist David Reich</a> helped oversee the study along with <a href="https://naturalhistory.si.edu/staff/douglas-owsley">Douglas Owsley</a>, curator of Biological Anthropology at the Smithsonian. The Smithsonian’s National Museum of Natural History is the custodian of the remains, while scientists at Reich&#8217;s lab handled the extraction and testing of the DNA.&nbsp;



“Our study combines for the first time two transformative developments in genomics in the last decade: ancient DNA technology, which makes it possible to efficiently sequence whole-genome data from human remains, and direct-to-consumer genetic databases that contain data from millions of people who have consented to participate in research,” <a href="https://hms.harvard.edu/news/historical-dna-study-connects-living-people-enslaved" target="_blank" rel="noreferrer noopener">said Reich</a>, co-senior author as well as a professor of genetics in the Blavatnik Institute at Harvard Medical School and professor of human evolutionary biology in Harvard’s FAS.



“This work demonstrates the power of DNA to provide information about ancestral origins,” he added.



Harney, who completed her PhD in Reich’s lab before joining 23andMe to facilitate this collaboration, and other 23andMe researchers designed and implemented an approach to compare the genomes of the Catoctin individuals with DNA from over 9 million 23andMe customers who consented to participate in research. As a result, the scientists identified more than 42,000 living relatives. Most of these relatives are distant, and a much smaller proportion have a closer relationship. The closest matches were likely 5th-degree relatives, equivalent to a great, great, great grandchild.



<figure class="wp-block-image aligncenter size-full"><img loading="lazy" decoding="async" width="873" height="486" src="http://35.88.189.111/wp-content/uploads/2023/07/Catoctin_heatmaps.jpg" alt="A Heat Map of the United States showing the geographic distribution of genetic relatives of the Catoctin Furnace Individual. The location of the furnace site is starred in Maryland." class="wp-image-31984" srcset="https://blogcms.23andme.com/wp-content/uploads/2023/07/Catoctin_heatmaps.jpg 873w, https://blogcms.23andme.com/wp-content/uploads/2023/07/Catoctin_heatmaps-300x167.jpg 300w, https://blogcms.23andme.com/wp-content/uploads/2023/07/Catoctin_heatmaps-768x428.jpg 768w" sizes="auto, (max-width: 873px) 100vw, 873px" /></figure>



<h6 class="wp-block-heading">Ethical Considerations</h6>



Studies like this are extremely delicate, not only because it is sometimes difficult to extract DNA from bones, but also because of the ethical questions this type of genetic analysis raises, especially when it comes to people who lived recently enough that they are almost surely closely related to individuals and communities today. As part of this work, the researchers have outline the ethical considerations &nbsp;<a href="https://www.cell.com/ajhg/fulltext/S0002-9297(23)00212-4" target="_blank" rel="noreferrer noopener">in a companion paper published in the&nbsp;American Journal of Human Genetics</a>. In addition, there is <a href="https://blog.23andme.com/articles/historical-dna-connection-to-early-enslaved-and-free-african-americans" target="_blank" rel="noreferrer noopener">an Q&amp;A published on the blog </a>from study co-author&nbsp;<a href="https://reich.hms.harvard.edu/people/roslyn-curry" target="_blank" rel="noreferrer noopener">Roslyn Curry</a>, a Harvard Kenneth C. Griffin Graduate School of Arts and Sciences student in the Reich lab and former 23andMe intern.



Typically, before work would begin on a DNA analysis like this, scientists would consult with relatives or local communities. But when this study started, there were no known family members of the enslaved people from the Catoctin Furnace site to consult. Instead, the <a href="https://catoctinfurnace.org/">Catoctin Furnace Historical Society</a> consulted with members of the <a href="https://aarchsociety.org/">African American Resources, Cultural and Heritage Society</a> in Frederick, Maryland. Later, archival researchers at the Catoctin Furnace Historical Society identified descendants of two African Americans who labored at the site, one free and the other enslaved. These descendant families also were consulted and expressed strong support for the project.&nbsp;



“This study represents a step toward meeting our ultimate goal of identifying a Catoctin descendant community using DNA and other tools,” said Elizabeth Comer of the Catoctin Furnace Historical Society.



<figure class="wp-block-image size-full"><img loading="lazy" decoding="async" width="614" height="352" src="http://35.88.189.111/wp-content/uploads/2023/08/TimelineFigure.png" alt="A timeline of the Catoctin Furnace from 1774 and 1903 when the furnace closed." class="wp-image-32017" srcset="https://blogcms.23andme.com/wp-content/uploads/2023/08/TimelineFigure.png 614w, https://blogcms.23andme.com/wp-content/uploads/2023/08/TimelineFigure-300x172.png 300w" sizes="auto, (max-width: 614px) 100vw, 614px" /></figure>



<h6 class="wp-block-heading">African American History and Connections</h6>



Collaborators on the study also included Boston University’s Linda Heywood and John Thornton, who have extensive expertise on African American history and culture. Also instrumental in the work was Harvard&#8217;s <a href="https://hutchinscenter.fas.harvard.edu/henry-louis-gates-jr">Henry Louis Gates Jr.</a>, the Alphonse Fletcher University Professor and Director of the Hutchins Center for African and African American Research at Harvard and host of the genealogy and genetics TV show Finding Your Roots.&nbsp;



“Recovering African American individuals’ direct genetic connections to ancestors heretofore buried in the slave past is a giant leap forward both scientifically and genealogically, opening new possibilities for those passionate about the search for their own family roots,” said Gates who is also a co-author of the paper.&nbsp;



<h6 class="wp-block-heading">History Revealed</h6>



Like hundreds or thousands of African American burial grounds across the country, the history of those who were buried at Catoctin Furnace could easily have been lost. There were no inscribed headstones, and many of the stones that marked the graves had been moved. The forgotten burial ground at Catoctin Furnace was first unearthed in the 1970s during construction of a new highway in Frederick County, Maryland, and the remains were placed in the care of the Smithsonian.



The history of the iron furnace is well documented. It was founded near a site that was naturally rich in iron ore with an extensive surrounding forest as a source of charcoal. The first owner of the furnace was Thomas Johnson Jr. —&nbsp; a wealthy enslaver, the first non-colonial governor of Maryland, and a signer of the <a href="https://www.ushistory.org/declaration/related/assoc74.html">Articles of Association</a>, a precursor document to the Declaration of Independence. Iron production began in earnest in 1776. It contributed in an important way to the arming of the fledgling Continental Army — supplying 100 tons of shells for the Siege of Yorktown. 



<figure class="wp-block-image aligncenter size-large"><img loading="lazy" decoding="async" width="1024" height="682" src="http://35.88.189.111/wp-content/uploads/2023/08/Catoctin_Furnace_in_Cunningham_Falls_State_Park_MD-1024x682.jpg" alt="A photo of the Remains of Isabella, an iron furnace, part of Catoctin Furnace in Cunningham Falls State Park, Maryland, USA." class="wp-image-32020" srcset="https://blogcms.23andme.com/wp-content/uploads/2023/08/Catoctin_Furnace_in_Cunningham_Falls_State_Park_MD-1024x682.jpg 1024w, https://blogcms.23andme.com/wp-content/uploads/2023/08/Catoctin_Furnace_in_Cunningham_Falls_State_Park_MD-1180x786.jpg 1180w, https://blogcms.23andme.com/wp-content/uploads/2023/08/Catoctin_Furnace_in_Cunningham_Falls_State_Park_MD-300x200.jpg 300w, https://blogcms.23andme.com/wp-content/uploads/2023/08/Catoctin_Furnace_in_Cunningham_Falls_State_Park_MD-768x511.jpg 768w, https://blogcms.23andme.com/wp-content/uploads/2023/08/Catoctin_Furnace_in_Cunningham_Falls_State_Park_MD-880x586.jpg 880w" sizes="auto, (max-width: 1024px) 100vw, 1024px" /><figcaption class="wp-element-caption">Remains of Isabella, an iron furnace, part of Catoctin Furnace in Cunningham Falls State Park, Maryland, USA.</figcaption></figure>



<h6 class="wp-block-heading">Early Industrialization in the United States</h6>



The furnace grew over time during the early stages of industrialization in the United States. By about 1840, immigrant laborers replaced the enslaved workforce at the facility. While the furnace remained in operation until the early 1900s, the critical contributions of Catoctin’s enslaved and free African American workforce was largely forgotten.



The site serves as an early example of industrialization, and provides an example of the contributions of enslaved people in the early industrial workforce in the United States. Laborers first dug the ore out of the ground, washed it, and then transported it to the furnace on carts. The furnace itself ran nonstop for months at a time. The fires were fueled using charcoal made by burning trees felled nearby, and then burned in large mounds that were tended by “colliers.” Beyond the work related to the furnace, enslaved people also worked in the area as domestic and farm laborers.



In <a href="https://repository.si.edu/handle/10088/102025">previous studies</a>, anthropologists at the Smithsonian were able to identify physical ailments from which the Catoctin individuals suffered through examination of their skeletal remains, such as a hip deformity that left one young woman with a lifelong limp, a man with a bent and fused spine, and a teenager with multiple, compressed vertebrae, likely due to heavy manual labor. The scientists also found high levels of zinc in the bones of one individual, likely caused by the industrial process of cleaning accumulated zinc deposits from inside the furnace stack.



In this study, DNA analysis found evidence suggesting that three individuals may have suffered from or been carriers of sickle cell anemia, caused by the HbS variant in the HBB gene.



<h6 class="wp-block-heading" id="h-connecting-families">Connecting Families</h6>



Connecting these unnamed enslaved people to living relatives, and thereby shedding new light on their ancestral origins and genetic legacy, was only possible with access to a diverse genetic database like 23andMe’s.&nbsp;This study offers additional insight into the genetic legacy of the enslaved and free people who labored at Catoctin Furnace. Combined with a study 23andMe completed in 2020 looking at the genetic impact of the <a href="https://www.cell.com/ajhg/fulltext/S0002-9297(20)30200-7">Transatlantic Slave Trade</a>, there is an increased understanding of the impact of slavery on those in bondage, their descendants, and their unacknowledged contributions to American history.

A conceptual image of DNA and a tree with the words A Hidden History Revealed

DNA Connections to Early Enslaved and Free African Americans

A heat map showing not just where living genetic relatives of the Catoctin Furnace are in the United States but also the ancestral contributions from Africa and Europe.

Roslyn Curry

Ethics and the Study of Historic DNA of African Americans Buried at the Catoctin Furnace

Editor&#8217;s note: This post has been slightly edited since being posted in 2013.
By David Tran
Look at your hands. Is your ring finger longer than your index finger, or vice versa?
The length of a person’s index finger relative to his or her ring finger may tell us something about that individual&#8217;s exposure to <a href="http://www.psychologytoday.com/articles/200612/the-sex-hormone-secrets">sex hormones</a> when he or she was still in the womb. But genetics also plays a big role here and recent studies are shedding light on the interplay between all these factors.
<div style="float: right; text-align: justify; width: 300px; background-color: #eee; padding: 10px; margin-left: 15px; margin-bottom: 15px; font-size: 12px;">
<img loading="lazy" decoding="async" class="aligncenter size-medium wp-image-18878" src="https://blog-api.23andme.com/wp-content/uploads/2013/08/digit-ratio-histogram-flat11-300x270.jpg" alt="digit ratio histogram flat(1)" width="300" height="270" srcset="https://blogcms.23andme.com/wp-content/uploads/2013/08/digit-ratio-histogram-flat11-300x270.jpg 300w, https://blogcms.23andme.com/wp-content/uploads/2013/08/digit-ratio-histogram-flat11-768x692.jpg 768w, https://blogcms.23andme.com/wp-content/uploads/2013/08/digit-ratio-histogram-flat11-880x793.jpg 880w, https://blogcms.23andme.com/wp-content/uploads/2013/08/digit-ratio-histogram-flat11.jpg 900w" sizes="auto, (max-width: 300px) 100vw, 300px" />
This graph shows the estimated distribution of people with different index to ring finger length ratios (X-axis). There&#8217;s a small but consistent pattern where women tend to have larger ratios. 

</div>
While this may seem trivial, understanding how genetics and environmental factors influence finger length may give us insight into important biological functions.
<h2>Finger Length</h2>
It may help us understand not just bone development but also other seemingly unrelated traits and conditions. Recent studies show that people with autism tend to have a smaller index-to-ring finger ratio. In contrast, other studies have suggested associations between finger length ratio and prostate cancer, obesity, ADHD, and sexual orientation.
These findings are still preliminary; however, more research is needed.
Finger lengths have fascinated scientists for a long time.
<h2>Sex Differences</h2>
As early as 1875, researchers knew there was a difference between the sexes. For many women, the index finger is nearly the same length as the ring finger, while in men, the ring finger tends to be longer than the index finger.
On average, a woman&#8217;s index finger is about <a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=20303062">97-98 percent</a> the length of her ring finger, while a man&#8217;s index finger is about <a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=20303062">96-97 percent</a>. A ratio of 100 percent means your index finger is the same length as your ring finger.
<h2>Ratios</h2>
One thing to be aware of is that ratios can vary significantly between the left and right hands, so researchers often take the average of both hands.
These are not ironclad rules, so if your index to ring finger length ratio seems different from the average, don&#8217;t worry. Many people have a larger or smaller ratio. (See the accompanying graph for an estimation of the distribution of people with different finger ratios.)
You can see a lot of overlap between the sexes and changes in the ratios. Ratios change from person to person and may also be influenced by <a href="https://www.ncbi.nlm.nih.gov/pubmed/18433004">ancestry</a>.
<h2>The Genetics of Finger Length</h2>
<div style="float: right; text-align: justify; width: 210px; background-color: #eee; padding: 10px; margin-left: 15px; margin-bottom: 15px; font-size: 12px;">
<img loading="lazy" decoding="async" class="aligncenter size-medium wp-image-18880" src="https://blog-api.23andme.com/wp-content/uploads/2013/08/finger-photo-191x300.jpg" alt="finger photo" width="191" height="300" srcset="https://blogcms.23andme.com/wp-content/uploads/2013/08/finger-photo-191x300.jpg 191w, https://blogcms.23andme.com/wp-content/uploads/2013/08/finger-photo-653x1024.jpg 653w, https://blogcms.23andme.com/wp-content/uploads/2013/08/finger-photo-561x880.jpg 561w, https://blogcms.23andme.com/wp-content/uploads/2013/08/finger-photo-752x1180.jpg 752w, https://blogcms.23andme.com/wp-content/uploads/2013/08/finger-photo.jpg 765w" sizes="auto, (max-width: 191px) 100vw, 191px" />
Two volunteers from 23andMe allowed us to measure their fingers and you can see in the picture that the man has a 95% ratio while the woman has a 98% ratio. 

</div>
In 2013, a team led by John Mollon at Cambridge University in England <a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=23263445">reported</a> that the single nucleotide polymorphism (SNP) was associated with a finger length ratio in people of European ancestry.
One genotype was associated with a 0.8 percent increase in finger length ratio. Another was associated with a 0.8 percent decrease in finger length ratio. The SNP lies near the SMOC1 gene, which is known to regulate bone growth and has been hypothesized to control finger length growth. Independent studies have suggested that the activity of the SMOC1 gene is controlled by <a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=18794802">testosterone</a> and <a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=17032503">estrogen</a> levels.
<h2>More Findings</h2>
In 2010, a <a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=20303062">study</a> found that another SNP is associated with a 0.6 percent increase in finger length ratio. This SNP lies near the LIN28B gene, which is important for the development of the embryo and a key player in stem cell development. However, how sex hormones affect LIN28B is less clear.
Many researchers are interested in finger-length ratios because they may shed light on exposure to sex hormones in the womb. Some studies suggest that exposure to more estrogen than testosterone is linked to larger finger-length ratios, while more testosterone has the opposite effect, leading to smaller finger-length ratios.
<h2>Learn More</h2>
Find out if your <a href="https://www.23andme.com/test-info/genetic-health/">genetics</a> might Increase your risk for any health conditions with 23andMe.

Research — Page 7