With apologies to Walt Whitman, we all contain multitudes … of microbial cells, trillions of microorganisms that live in and on our bodies.



The<a href="https://www.genome.gov/genetics-glossary/Microbiome"> human microbiome</a> is vast and varied and accompanies us through our lives, changing as we age. As scientists continue to learn more about these microscopic ecosystems on our skin, mouths, and gut, we understand more and more about the sometimes surprising role they play in our health.



Researchers at 23andMe, in collaboration with the Michael J. Fox Foundation, recently published a study in <a href="https://www.nature.com/articles/s43856-024-00630-8">Communications Medicine</a> looking at the gut and oral microbiome of people with Parkinson’s disease. The study offers intriguing new insights that could help diagnose and monitor disease development and progression earlier.



“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,” said Keaton Stagaman, PhD, a postdoctoral research scientist at 23andMe and a co-author of the study.



<h2 class="wp-block-heading" id="h-gut-brain-axis">Gut-Brain Axis</h2>



Parkinson’s is a neurodegenerative disorder that affects movement and cognitive function. Research has found a strong ‘gut-brain axis’ that connects the central nervous system to the gastrointestinal tract, and studies have recently pointed to the potential link between Parkinson’s disease and the gut microbiome.



Along with Parkinson’s, changes in the gut microbiome have been linked to other conditions, including<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10012812/"> inflammatory bowel disease</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9657115/">Clostridium difficile infections</a>,<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6300652/"> autoimmune disorders</a>,<a href="https://hms.harvard.edu/news/changes-gut-microbiome-may-increase-type-2-diabetes-risk"> diabetes</a>, and obesity. The links are intriguing but not yet fully understood. That said, a better understanding of the microbiome and its role could be essential for diagnosing and treating many conditions.



The new research by 23andMe offers more evidence of the connection between Parkinson’s and changes in the gut microbiome.



<h2 class="wp-block-heading" id="h-different-types-of-microorganisms">Different Types of Microorganisms</h2>



For this study, scientists used microbiome data from saliva and stool samples of people with and without Parkinson’s disease.



Scientists have identified about 1,000 microbial species in the human mouth, whereas the human gut has the densest collection of microorganisms in the body.<a href="https://www.ncbi.nlm.nih.gov/books/NBK562894/"> According to the National Institutes</a> of Health, the large intestine has as many as 100 billion to one trillion cells per milliliter and is among the densest microbial ecosystems ever observed.



<figure class="wp-block-image aligncenter size-large"><img loading="lazy" decoding="async" width="1024" height="896" src="http://35.88.189.111/wp-content/uploads/2024/10/suppFig4_withinSources_functional_corr_network_KO_v1-1024x896.png" alt="" class="wp-image-33430" srcset="https://blogcms.23andme.com/wp-content/uploads/2024/10/suppFig4_withinSources_functional_corr_network_KO_v1-1024x896.png 1024w, https://blogcms.23andme.com/wp-content/uploads/2024/10/suppFig4_withinSources_functional_corr_network_KO_v1-300x263.png 300w, https://blogcms.23andme.com/wp-content/uploads/2024/10/suppFig4_withinSources_functional_corr_network_KO_v1-768x672.png 768w, https://blogcms.23andme.com/wp-content/uploads/2024/10/suppFig4_withinSources_functional_corr_network_KO_v1-880x770.png 880w, https://blogcms.23andme.com/wp-content/uploads/2024/10/suppFig4_withinSources_functional_corr_network_KO_v1-1180x1033.png 1180w" sizes="auto, (max-width: 1024px) 100vw, 1024px" /><figcaption class="wp-element-caption">Images showing the clustering of different families of microorganisms from the gut and saliva of people with and without Parkinson&#8217;s disease. </figcaption></figure>



Because of the vast number of different microorganisms, 23andMe scientists in this research used sequence data to group those organisms into Operational Taxonomic Units or closely related types of bacteria. Using these groupings, the scientists were able to find significant differences in the type and abundance of microorganisms in the microbiome of people with Parkinson’s when compared to those without the disease.



This was the case in both stool and saliva samples. This is significant and suggests that using saliva samples, which are much simpler for patients and scientists to collect, is adequate for detecting differences in the microbiome for those with Parkinson’s.



<h2 class="wp-block-heading" id="h-the-findings">The Findings</h2>



In undertaking the study, the researchers thought there might be distinct microbial changes in people with Parkinson’s and that those changes could be seen in the early stages of the disease before many symptoms develop.



Among the signature differences researchers found was a higher diversity of microbes within the microbiome of those with Parkinson’s. This was the case even when considering other things that could affect the diversity of microbes, such as oral hygiene or constipation. In addition, the researchers said that the amount and diversity of microbes in samples was a good predictor of whether someone had Parkinson’s disease. Using a well-known machine learning algorithm called Random Forest, the team could predict whether a person had Parkinson’s or not 80 percent of the time.



The researchers also identified specific types of bacteria that differed between people with Parkinson’s and those who did not have the disease. The scientists believe that the findings might help find specific markers in the microbiome, specifically in saliva samples, that could be used to monitor for early signs of the disease.



Other studies have shown that changes in the gut microbiome may offer early indications of the onset of changes in a person’s motor functions.



<h2 class="wp-block-heading" id="h-learn-more">Learn More</h2>



Beyond the ability to use a person’s microbiome to evaluate the status of Parkinson&#8217;s, the paper also suggests that altering a person’s microbiome may offer another avenue for treating Parkinson’s symptoms. 



You can read the complete study in <a href="https://www.nature.com/articles/s43856-024-00630-8">Communications Medicine here.</a> 



Additionally, data from the Fox Insight PD Microbiome sub-study are available to qualified researchers <a href="https://foxden.michaeljfox.org/insight/explore/insight.jsp">here</a>.

23andMe Blog

23andMe Blog Team

Parkinson’s and the Microbiome

A new study by scientists in New Zealand determined that genetics has a much more significant impact on the risk of developing gout than previously thought.



Led by researchers at the University of Otago in New Zealand, the study published in the journal <a href="https://www.nature.com/articles/s41588-024-01921-5">Nature Genetics</a> used data from more than 2.6 million people with about 75 percent of that data from 23andMe customers who consented to participate in research.



<h2 class="wp-block-heading" id="h-ending-the-stigma">Ending the Stigma</h2>



While diet and lifestyle play a role, genetics have an outside influence on whether a person will develop <a href="https://www.23andme.com/topics/health-predispositions/gout/">gout</a>, this painful form of arthritis caused by the build-up of uric acid.



“Gout is a chronic disease with a genetic basis and is not the fault of the sufferer – the myth that gout is caused by lifestyle or diet needs to be busted,” said Professor Tony Merriman of Otago’s Department of Microbiology and Immunology, and the leading author of the paper.



Once associated with the gluttonous indulgence of someone like King Henry VIII, the researchers said they hoped that their study would illuminate the complicated biology of the disease and dispel some of the stigma around gout.



“This widespread myth causes shame in people with gout, making some people more likely to suffer in silence and not go and see the doctor to get a preventive drug that lowers urate in the blood and will prevent their pain,” Merriman said.&nbsp; 



<h2 class="wp-block-heading" id="h-genes-and-environment">Genes and Environment </h2>



As with many diseases, many factors influence the risk of developing gout. 



“People need to understand that while specific dietary factors — such as eating red meat — can trigger gout attacks, the fundamental&nbsp;cause&nbsp;is high urate levels, crystals in the joints, and an immune system primed to ‘attack’ the crystals – genetics plays an important role in all of these processes.”



The study identified 377 variants associated with gout, and 148 of those associations were identified for the first time. 



Many of these genetic variants are in or near gene regions involved in regulating urate levels and the mechanisms by which elevated uric acid in the blood, something called hyperuricemia, progresses to inflammation in the joints with gout. The study also identified several genes in the immune response associated with gout.



You can read the complete study in <a href="https://www.nature.com/articles/s41588-024-01921-5" target="_blank" rel="noreferrer noopener">Nature Genetics here</a>.

New Genetic Research on Gout

In the largest genetic study of its kind to date, 23andMe scientists have identified variants associated with an increased risk of developing Long COVID and also established a genetic link between the potentially debilitating condition and other chronic conditions such as depression, chronic fatigue syndrome, and fibromyalgia.



Published in the preprint server for health scientists known as <a href="https://www.medrxiv.org/content/10.1101/2024.10.07.24315052v1">MedRxiv</a>, the study suggests that genetic differences in how the body&#8217;s immune system recognizes and responds to the virus likely influence the chances of developing Long COVID. Among the strongest genetic associations was in the region of the HLA-DRB1 gene, which plays a critical role in the body&#8217;s immune response.



&#8220;Long COVID&#8217;s rising burden and impact highlights the urgent need to better understand its pathophysiology. Our study marks a significant step toward unraveling the genetic underpinnings of Long COVID where we report that the immune function may play an important role in developing the condition,” said Ninad Chaudhary, PhD, a postdoctoral fellow at 23andMe and a co-author of the study.&nbsp; “Along with identifying robust evidence that individual genetic variants contribute to the risk of Long COVID, we also identify potential causal effects of genetic predisposition to depression, chronic fatigue syndrome, and fibromyalgia with the development of Long COVID. This provides opportunities to identify at-risk individuals and new avenues of investigation for investigating treatments that may address the impact of Long Covid.&#8221;



<h2 class="wp-block-heading" id="h-what-is-long-covid">What is Long COVID?</h2>



The <a href="https://www.cdc.gov/covid/long-term-effects/index.html">US Centers for Disease Control and Prevention defines Long COVID</a> as being a chronic condition lasting three months or more after an initial infection COVID-19.



Individuals suffering from Long COVID present with a wide range of more than 200 symptoms, but among the most common are brain fog, fatigue, and shortness of breath. Estimates suggest that worldwide, as many as 65 million people endure Long COVID.



A little over 7 percent of people infected with COVID-19 will develop Long COVID, while more than half of those with severe cases will develop the lingering condition. Projecting over the millions of individuals worldwide who&#8217;ve been infected or are yet to be re-infected, the public health impact of Long COVID is likely to linger for years to come. Understanding the underlying biology and associations may help scientists understand how to treat the condition better.



<h2 class="wp-block-heading" id="h-immune-response-and-blood-type">Immune Response and Blood Type</h2>



In addition to the HLA finding, 23andMe scientists also focused on the role of the ABO gene, which determines a person&#8217;s blood type. The role of the ABO gene has been previously identified by 23andMe scientists and others for its role in the severity of COVID-19 in some individuals. In this study, the scientists suggest that blood type or ABO variation may also influence the likelihood of developing Long COVID.&nbsp;



The ABO blood group also has a role in immune response as well as influences the factors that affect the coagulation of blood. This, in turn, may explain why it is associated with both acute COVID-19 and Long COVID cases. The blood types determined by the ABO gene are also linked to blood clotting and inflammation, both hallmarks of Long COVID.



The scientists working on this study also identified several new associations in or near the genes BPTF, C17orf58, and KPNA2. Researchers believe these genes&#8217; role in susceptibility to Long COVID is also related to the defense system against viruses.



<h2 class="wp-block-heading" id="h-chronic-conditions-associated-with-long-covid">Chronic Conditions Associated with Long COVID</h2>



This study also found strong genetic correlations between Long COVID and several other chronic conditions, including chronic fatigue syndrome, fibromyalgia, and depression. The researchers found that people with genetic predispositions toward these chronic conditions were more likely to develop Long COVID after a COVID-19 infection.



For researchers, the link between these chronic conditions could provide clues to the underlying biology why Long COVID develops in some people and not others. For example, immune dysregulation and impaired cellular function, which may play a role in Long COVID, are often hallmarks of chronic fatigue syndrome and fibromyalgia.&nbsp;



Other studies have shown how depression affects immune function and the body&#8217;s ability to fight off infections. The genetic link between depression and Long COVID may support the idea that immune system dysfunction plays a central role in the development of Long COVID.



<h2 class="wp-block-heading" id="h-implications-for-future-research-and-treatment">Implications for Future Research and Treatment</h2>



By identifying new genetic associations for Long COVID and possible biological pathways, the research could help other scientists search for treatments. For example, existing medicines used to treat depression might have clinical utility in treating Long COVID if well-powered randomized controlled trials of these medicines in the Long COVID setting were to substantiate this hypothesis.



In addition, the research may help identify those at most risk for Long COVID, who could benefit from better monitoring post infection or better treatment options.



Ultimately, the genetic insights from this study provide a foundation for future research that could lead to improved care and outcomes for Long COVID patients. As we continue to learn more about the condition, we hope that we will soon have better tools to prevent and treat the long-term effects of COVID-19, bringing relief to the millions of people affected by this condition worldwide.



This <a href="https://www.medrxiv.org/content/10.1101/2024.10.07.24315052v1">study</a> is part of a series being conducted by 23andMe scientists since the beginning of the pandemic in 2020, and it was made possible by 23andMe customers who consented to participate in research.

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

Genetic Associations with Long COVID

In the largest and most diverse genetic study of sickle cell trait, researchers from 23andMe, the National Institutes of Health, and Johns Hopkins University School of Medicine published findings linking the trait to increased risk for certain blood clots.



<h2 class="wp-block-heading" id="h-blood-clotting-risks">Blood Clotting Risks</h2>



The study, published just as we begin National Sickle Cell Awareness Month, validated the association of sickle cell trait with blood clots. But to put this risk into context,<a href="https://ashpublications.org/bloodadvances/article/doi/10.1182/bloodadvances.2024014252/517723/Ancestry-Independent-Risk-of-Venous"> the study</a>, which included data from more than four million people who consented to participate in research, found that people with a genetic variant known as Factor V Leiden are at a higher risk for developing harmful blood clots or<a href="https://www.23andme.com/topics/health-predispositions/hereditary-thrombophilia/"> venous thrombosis (VTE)</a> compared to those who are carriers of <a href="https://www.cdc.gov/sickle-cell/sickle-cell-trait/index.html">sickle cell trait</a>.  



The study also looked at different types of blood clots, like deep vein thrombosis, which forms in a deep vein, like in the legs, and pulmonary emboli, which are caused by blood clots that travel to the lungs. This study validated the association between having sickle cell trait and developing pulmonary emboli. It did not find an association with developing deep vein thrombosis. The research also confirmed the association between Factor V Leiden and pulmonary emboli and deep vein thrombosis.



“This study, therefore, provides important insights about patterns of venous blood clots and suggests a unique mechanism of blood clotting in people with sickle cell trait,” said Rakhi Naik, M.D. M.H.S., clinical director for the Division of Hematology at Johns Hopkins University, Baltimore, who co-led the study. “Knowing the risks of blood clots in people with sickle cell trait is important for situations such as surgeries or hospitalizations, which add to the risk of developing serious blood clots.”&nbsp;



<h2 class="wp-block-heading" id="h-ancestry-independent-risks">Ancestry-Independent Risks</h2>



The findings published in the <a href="https://ashpublications.org/bloodadvances/article/doi/10.1182/bloodadvances.2024014252/517723/Ancestry-Independent-Risk-of-Venous">journal Blood Advances</a> are significant because the number and diversity of research participants allowed scientists to calculate “ancestry-independent” odds ratios for the risk of blood clotting among those with sickle cell trait.



More than 200,000 of the four million research participants were of African ancestry, 590,000 were of Latino ancestry, three million were of European ancestry, 150,000 were of East Asian ancestry, and 41,000 were of South Asian ancestry.



Although the trait is most common among people of African ancestry, with an estimated eight to 10 percent of African Americans having sickle cell trait, it can also affect Latinos, South Asians, and people with ancestry from southern Europe and the Middle East. More than 100 million people worldwide have sickle cell trait.



<h2 class="wp-block-heading" id="h-the-importance-of-diversity-in-genetic-research">The Importance of Diversity in Genetic Research</h2>



Vence Bonham Jr., J.D., who co-led the study and serves as&nbsp;acting Deputy Director of the<a href="https://www.genome.gov/"> National Human Genome Research Institute</a> (NHGRI) at the<a href="https://www.nih.gov/">&nbsp; National Institutes of Health</a>, United States, said The study offers another example of the importance of using a diverse population in genetic research.



Bonham has led sickle cell disease research at the NHGRI and pushed for broader inclusion of underrepresented groups in genomics research. He’s also led the<a href="https://www.genome.gov/research-at-nhgri/Projects/Democratizing-Education"> Democratizing Education for Sickle Cell Disease Gene Therapy Project</a>, offering resources for those with sickle cell disease to better understand treatment options. In 2018, Naik and Bonham published a systematic review examining the health complications associated with sickle cell trait. This&nbsp;current study expands on that previous work by measuring the risk of developing blood clots.



“Because sickle cell trait is often associated with people who identify as Black or African&nbsp; American, it is not widely studied in other populations, which has created an information gap that may lead to unintended harm for those with sickle cell trait,” Bonham said. “In particular, the racialization of sickle cell trait has resulted in poor estimations of health risks. The results of our study will help clinicians properly contextualize the&nbsp; risk of blood clots amongst people with sickle cell trait without unintended bias.”



Too often, the blood clotting risks associated with sickle cell trait are assumed to be relevant only to people of African ancestry. In contrast, the risks associated with Factor V Leiden are thought to only be relevant to those of European ancestry, said Julie Granka, PhD, a Principal Scientist at 23andMe and a co-author of the paper.



That kind of bias can also lead to harmful assumptions about blood clotting.



“Our findings demonstrate that sickle cell trait is present in people of many different ancestries and confers similar risks for blood clotting,” Granka said. “This study can provide clinicians with valuable information for guidance for individuals who have sickle cell trait &#8212; both across ancestries, as well as in comparison to Factor V Leiden, where more guidance exists.”&nbsp;



The new research also replicates some of the health risks associated with having sickle cell trait found in other studies, specifically the association with pulmonary emboli.



The size and scale of this study, compared to past research that included data from just a few thousand individuals, allowed researchers to provide more precise risk estimates within different populations. Moving forward with this ongoing work, the researchers are currently looking at the risk of blood clots for sickle cell trait carriers during pregnancy.&nbsp;



<h2 class="wp-block-heading" id="h-raising-awareness-of-sickle-cell-trait">Raising Awareness of Sickle Cell Trait</h2>



Having sickle cell trait means that a person has one copy of the HbS variant in the HBB gene. Unlike sickle cell anemia—a serious condition caused by having two copies of the HbS variant—people who carry just one copy of HbS do not usually have any health problems and are not at risk of developing sickle cell anemia.&nbsp;



Further research and clinical guidance are still needed to better understand the potential health risks and complications someone with sickle cell trait may experience. Knowing whether you have sickle cell trait is essential for family planning. If a person with sickle cell trait has a child with a partner who also has a variant in their HBB gene, each of their children has a 25 percent chance of having sickle cell disease.&nbsp;



Independent of this collaboration, 23andMe has collaborated on a<a href="https://www.23andme.com/sickle-cell/https:/www.23andme.com/sickle-cell-awareness-program/"> Sickle Cell Carrier Status Awareness Program</a> with the Morehouse College of Medicine, the<a href="https://www.sicklecellga.org/"> Sickle Cell Foundation of Georgia</a>,<a href="https://www.sc101.org/"> Sickle Cell 101</a>, and the<a href="https://www.btsscycle.org/"> Breaking the SSickle Cell Cycle</a> Foundation. The work includes promoting awareness of sickle cell disease and offering resources for individuals with sickle cell trait and disease.



Dr. Lametra Scott, founder of Breaking the SSickle Cell Cycle and sickle cell advocate, shared about the study: &#8220;The increased risk of venous thromboembolism (VTE) and pulmonary embolism (PE) in sickle cell trait (SCT) underscores the importance of learning one&#8217;s SCT status and the value the Sickle Cell Carrier Awareness Program brings to the community.&#8221;



<h2 class="wp-block-heading" id="h-find-out-more">Find Out More</h2>



Knowing whether you have sickle cell trait is a crucial first step in family planning.



23andMe’s Health + Ancestry Service includes a<a href="https://www.23andme.com/topics/carrier/sickle-cell-anemia/"> Sickle Cell Anemia Carrier Status report.</a>* This allows participants to learn their carrier status. 23andMe’s report provides extensive information about what it means to be a sickle cell trait carrier.



In addition, 23andMe worked with the non-profit Sickle Cell 101 to offer those with questions about the condition the opportunity to seek additional information and counseling after receiving results on the largest global online platform for sickle cell education, awareness, and research.



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



<h2 class="wp-block-heading" id="h-note">Note:</h2>



*The 23andMe PGS test uses qualitative genotyping to detect select clinically relevant variants in the genomic DNA of adults to report carrier status and reporting and interpreting genetic health risks. The relevance of each report may vary based on ethnicity. Our carrier status reports can be used to determine carrier status, but cannot determine if you have two copies of any genetic variant. These carrier reports are not intended to tell you anything about your risk for developing a disease in the future or anything about the health of your fetus, or your newborn child’s risk of developing a particular disease later in life. For certain conditions, we provide a single report that includes information on both carrier status and genetic health risk. 



The Sickle Cell Anemia Carrier Status report is indicated for the detection of the HbS variant in the HBB gene. The report can tell you if you have two copies of the tested variant, and if you are at risk of developing symptoms of sickle cell anemia, but does not describe your overall risk of developing symptoms. The test is most relevant for people of African descent. It is also relevant for people of Middle Eastern and South Asian descent, as well as people from the Caribbean, the Mediterranean, and parts of Central and South America.



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

An illustration for 23andMe's Sickle Cell Carrier Statues Awareness Program.

New Genetic Research on Sickle Cell Trait

In the hunt for new medications where the odds are stacked against you, where fewer than one in ten drug programs succeed, you need an edge.



A new study by <a href="https://therapeutics.23andme.com/">23andMe’s Therapeutics</a> and Research teams builds upon<a href="https://www.nature.com/articles/s41586-024-07316-0"> previous research</a>, indicating that human genetic data offers that kind of advantage and doubles or triples the success rate of drug development. 



If you add improved gene mapping to your toolbox, as 23andMe has done for this study, the success rate improves by four or five times. Moreover, the <a href="https://blog.23andme.com/articles/the-power-of-large-genetic-datasets">sheer scale </a>of the 23andMe data ensures that genetic insights linking a drug target to disease are available for 60 percent more drug targets than from other resources. 



<figure class="wp-block-image aligncenter size-large"><img loading="lazy" decoding="async" width="1024" height="489" src="http://35.88.189.111/wp-content/uploads/2024/09/Genetic-Driven-Drug-Discovery-1024x489.png" alt="An illustration of genetic driven drug discovery from GWAS to Clinical Trials." class="wp-image-33337" srcset="https://blogcms.23andme.com/wp-content/uploads/2024/09/Genetic-Driven-Drug-Discovery-1024x489.png 1024w, https://blogcms.23andme.com/wp-content/uploads/2024/09/Genetic-Driven-Drug-Discovery-300x143.png 300w, https://blogcms.23andme.com/wp-content/uploads/2024/09/Genetic-Driven-Drug-Discovery-768x367.png 768w, https://blogcms.23andme.com/wp-content/uploads/2024/09/Genetic-Driven-Drug-Discovery-880x420.png 880w, https://blogcms.23andme.com/wp-content/uploads/2024/09/Genetic-Driven-Drug-Discovery-1180x564.png 1180w" sizes="auto, (max-width: 1024px) 100vw, 1024px" /></figure>



Traditional drug development is risky, time-consuming, and costly.<a href="https://www.nature.com/articles/s41598-019-54849-w"> Ninety percent</a> of drugs fail. All those failures add time and money to the process. That means that getting a drug approved costs, on average,<a href="https://jamanetwork.com/journals/jama/article-abstract/2762311"> about $1 billion</a> and takes more than a decade. Only about 50 new drugs are approved in an average year by the FDA. There were<a href="https://www.fda.gov/drugs/novel-drug-approvals-fda/novel-drug-approvals-2023"> 55 in 2023</a>, and so far this year, there have been 24. This is despite the billions spent each year by pharmaceutical companies on research and development for new medications.



<h2 class="wp-block-heading" id="h-a-massive-opportunity">A Massive Opportunity</h2>



Previous work has pointed to human genetics as one way to reverse this trend, and several companies are now relying on human genetics as a starting point for drug target discovery. We now show unequivocally that using human genetic data at scale could radically change the hunt for new drugs, helping to get new medicine to people who need it faster and more efficiently. 



&#8220;There&#8217;s still a massive amount of value left utilizing human genetics for <a href="https://blog.23andme.com/articles/drug-discovery-explained">drug development</a>,&#8221; said Adam Auton, Ph.D., Vice President of Human Genetics at 23andMe and a study co-author. &#8220;We&#8217;ve just scratched the surface, and the scale of the 23andMe dataset allows us to draw links between genes and disease that aren’t possible to find anywhere else. 23andMe continues to invest in new capabilities and computational approaches such as integrating artificial intelligence and machine learning into our discovery pipeline.&#8221;



The new study, released on<a href="https://www.medrxiv.org/content/10.1101/2024.06.17.24309059v1"> MedRxiv</a>, a preprint server for health scientists, offers a peek behind the curtain into 23andMe&#8217;s massive and powerful therapeutic research database. In this post, we hope to highlight some of its critical findings and illustrate how using human genetic data can support drug target discovery, target validation, and target de-risking in the drug development process.



“Traditional approaches to drug development are often a gamble, where nine out of ten programs fail. But with the scale and precision of 23andMe’s human genetic data, we&#8217;re changing the odds,&#8221; said Xin Wang, PhD, a 23andMe Therapeutics Senior Scientist and the lead author of the study. 



&#8220;Our study demonstrates that leveraging genetics can double or triple success rates and, when combined with advanced gene mapping, improve success by up to fivefold. Our methods ensure we&#8217;re targeting diseases more accurately and efficiently, bringing life-saving treatments to patients faster.&#8221;



<figure class="wp-block-embed aligncenter is-type-video is-provider-vimeo wp-block-embed-vimeo wp-embed-aspect-16-9 wp-has-aspect-ratio"><div class="wp-block-embed__wrapper">
<iframe loading="lazy" title="Genomics Unmuted: The impact on clinical success from the 23andMe cohort" src="https://player.vimeo.com/video/998331419?dnt=1&amp;app_id=122963" width="500" height="281" frameborder="0" allow="autoplay; fullscreen; picture-in-picture; clipboard-write"></iframe>
</div></figure>



<h2 class="wp-block-heading" id="h-size-amp-scale-why-big-is-better">Size &amp; Scale: Why Big is Better</h2>



23andMe has the world&#8217;s largest genetic and phenotypic database for therapeutic research. It&#8217;s vital to grasp the power of a resource of that scale.



For this study, 23andMe scientists used de-identified data from more than 7.5 million individuals who consented to participate in research. For perspective, that research cohort is almost twice the size of the combined total of all the major public biobanks worldwide.  Most of these biobanks number in the tens of thousands, while the largest are between 500,000 and one million. 23andMe has more than 15 million customers with genotype and phenotype information. More than 80 percent of 23andMe customers consent to participate in research and have contributed over 4 billion health and trait data points, including disease diagnosis, medication use, medication side effects, lifestyle, diet, and family health history.



Overall, the combined phenotypic and genetic data available for life sciences research from 23andMe is an order of magnitude larger than any other cohort.



The size and scale of 23andMe&#8217;s drug discovery database are critically important because they capture much more diversity. Having a diverse research database is essential for equity and because having enough data from people of different ethnicities helps discern genetic variants causing disease across these populations. Sometimes, a variant is more common in one population than in another. Including people of diverse ethnicities offers more potential to identify targets not easily identified in a more homogenous dataset.



Bigger is better because as the size of 23andMe&#8217;s database grows and as we apply new technologies like AI and machine learning to this massive dataset, researchers can find more genetic associations, leading to more potential drug targets.



<h2 class="wp-block-heading" id="h-gene-mapping-and-more-targets">Gene Mapping and More Targets</h2>



For example, the total number of target-indication pairs is 60 percent greater with 23andMe&#8217;s dataset than from public biobank data. A target-indication pair is the pairing of a specific condition or disease, known as ‘an indication,’ to a specific protein or biological ‘target.’ Identifying these target-indication pairs is an essential first step in drug discovery and development. As part of this study, 23andMe scientists found about 1,050 target-indication pairs for medically relevant conditions related to more than 41 disease categories, including different cancers, metabolic conditions, neurological conditions, and autoimmune diseases.



Just look at one of these conditions, asthma, to illustrate the power of size and scale. 23andMe has data for more than three million individuals within its asthma cohort — this includes those with asthma and those without the condition who are used as controls. From that cohort, researchers identified 652 significant genetic associations for asthma. For comparison, a <a href="https://www.cell.com/cell-genomics/pdf/S2666-979X(22)00165-3.pdf">2022 meta-analysis by researchers at the Broad Institute </a>included about 1.6 million individuals and identified 49 novel genetic associations among a total of 179 genetic associations found. 



The 652 significant genetic associations found for asthma is an example of one of more than 1,050 target-indication pairs for a medically relevant condition. In all, 23andMe scientists found more than 140,000 significant genetic associations for different common and rare conditions. That amounts to an average of 130 different genetic associations for each condition. In addition, those associations point to 15,007 genes associated with therapeutically relevant conditions, including 1,355 genes associated with conditions that scientists had not previously identified in public genetic studies. That amounts to about 5.9 to 18.8 novel indications per genetic association.



By adding gene mapping, scientists can more easily identify the likely causal gene for a genetic association and determine the mechanism for how a specific gene is related to a disease or condition. 23andMe researchers found that improved gene mapping methods from human genetic associations also improve relative success by four or five times. 



This is a potent tool for scientists who want more power in their work and offers a head start for those hunting for higher-confidence potential drug targets.



&#8220;The scale of the data enables me to perform studies in an afternoon at 23andMe that would have taken years in my previous academic life,&#8221; Auton once said about the research database.



<h2 class="wp-block-heading" id="h-from-gene-to-drug">From Gene to Drug</h2>



Traditional target-based drug discovery often doesn’t follow a direct path like a game of chutes and ladders. There are many dead ends, much trial and error, that might force researchers to scrap one target and start with another.



With a target identified, researchers can search for a compound that will hit that target. They then must test whether it is safe and effective. It must adequately bind to a specific disease-causing target in the body and trigger the correct response without affecting other parts of the body. If the drug has no effect or triggers an adverse reaction, the effort returns to square one. Each step in the process— from identifying the right target to finding a molecule or drug that will properly bind to that target to determining if that drug elicits the right response— is a potential point of failure.



However, using human genetic data offers an edge at each point, improving the potential for success. We’ve shown how human genetics dramatically boost the identification of a potential target; it can also enhance the chances of success at further steps in the process.&nbsp;



<h2 class="wp-block-heading" id="h-disease-subtypes">Disease Subtypes</h2>



But leveraging human genetic data isn’t just about boosting potential targets; it can also help in identifying disease subtypes and safety signals and identifying individuals best to recruit for clinical trials. Human genetic data can be used to identify disease subtypes, which may include different symptoms and progression and may also respond differently to a therapeutic. In addition, human genetic data can be used to identify safety signals, giving researchers more confidence that targeting a gene is safe. For example, with this large dataset, 23andMe researchers can identify individuals with a loss of function variant. Knowing that turning off that specific gene is not deleterious is incredibly important for drug development. Finally, researchers can use genetic data to help identify individuals for clinical trial recruitment who are most likely to respond to a therapeutic, further improving the chances for clinical trial success.



A drug target for an indication is not an actual target; it’s a potential target. Researchers must do additional work to determine if it is the right target for a specific condition. Making that determination is another crucial step that can be enhanced using human genetic data in gene mapping. Gene mapping is vital for understanding whether a potential target is relevant to a specific condition.



23andMe’s massive research data allows scientists to create a gene-mapping algorithm that, in turn, can improve the likelihood of clinical success of a drug target by four or five times, according to 23andMe’s new study. As part of this research, 23andMe scientists mapped 416 unique gene-trait associations, genes linked explicitly to about 190 different diseases or conditions.



Mapping a variant or drug target indication to a nearby gene is called “variant-to-gene mapping.” This “variant-to-gene mapping” helps researchers determine the most likely causal gene from a genetic association. Mapping that out involves using functional data—information on protein and molecular structures, data on biochemical interactions, and other data— to understand the link between a potential drug target and a specific health condition. 



Researchers use gene mapping to understand how a specific variant affects the function of a gene and its role in a disease or condition. Is it protective against a disease or condition, or is it causal? What happens if that gene expression is changed or turned on or off?



Rare variants offer another way of making these determinations because a rare variant precisely pinpoints causal genes at the point of a genetic association, something common variants don’t. In some cases, these rare variants might turn off gene expression, known as a “loss-of-function” variant. From a research standpoint, identifying these rare variants and understanding whether that loss of function is either deleterious or protective is incredibly powerful. Knowing that ahead of time gives researchers more confidence that targeting that variant is safe and or has the desired effect. One well-known example of this is a loss-of-function variant in the<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447476/"> PCSK9 gene that</a> lowers the level of LDL in the blood. That information has been used to develop cholesterol-lowering medications.



So, identifying rare variants offers researchers a shortcut for focusing on targets with the most promise for success. In addition, 23andMe researchers use machine learning to discern patterns in the data, match genes to diseases using genetic associations, and suggest possible useful drug candidates that match the target variants. 



<h2 class="wp-block-heading" id="h-the-human-genetic-advantage">The Human Genetic Advantage</h2>



For this research, 23andMe scientists analyzed trillions of data points to illustrate the advantage of adding human genetics in efficiently identifying drug targets, de-risking the drug development process, and dramatically boosting the probability of success.



The new study just scratches the surface of what is possible with this data resource&#8217;s vast scale and diversity. It also hints at what is possible when artificial intelligence and machine learning techniques are applied to this powerful human genetic database for drug discovery. 



“In an industry where just one in ten drugs make it to patients, the potential impact from what we’re doing at 23andMe and what our scientists have demonstrated with this paper could be game-changing,” said Auton. “We believe that 23andMe can enable the broader biotech industry to bring new drugs to patients faster and more cheaply. ”

A New Era for Human Genetic Data in Drug Development

Decisions about who should be screened for certain inherited conditions may hinge heavily on the patient’s self-reported ethnicity. 



However, a <a href="https://www.gimopen.org/article/S2949-7744(24)01015-X/fulltext">new study by 23andMe researchers </a>found that these ethnicity-based guidelines miss more than half of those who are carriers for some serious genetic conditions.



<figure class="wp-block-image alignright size-medium"><img loading="lazy" decoding="async" width="300" height="239" src="http://35.88.189.111/wp-content/uploads/2018/03/Carrier-Status-300x239.jpg" alt="" class="wp-image-26106" srcset="https://blogcms.23andme.com/wp-content/uploads/2018/03/Carrier-Status-300x239.jpg 300w, https://blogcms.23andme.com/wp-content/uploads/2018/03/Carrier-Status-768x612.jpg 768w, https://blogcms.23andme.com/wp-content/uploads/2018/03/Carrier-Status-1024x816.jpg 1024w, https://blogcms.23andme.com/wp-content/uploads/2018/03/Carrier-Status-880x701.jpg 880w, https://blogcms.23andme.com/wp-content/uploads/2018/03/Carrier-Status.jpg 1137w" sizes="auto, (max-width: 300px) 100vw, 300px" /></figure>



<h2 class="wp-block-heading" id="h-carrier-status-testing">Carrier Status Testing</h2>



Some medical societies, including the American College of Obstetricians and Gynecologists (ACOG), have traditionally recommended ethnicity-based carrier screening for specific inherited conditions. For example, for people reporting Ashkenazi Jewish ancestry, they recommend screening for such as <a href="https://www.23andme.com/topics/carrier/bloom-syndrome/">Bloom syndrome</a> and <a href="https://www.23andme.com/topics/carrier/gaucher-disease-type-1/">Gaucher disease</a>. For those with Ashkenazi ancestry or French Canadian or Canjun ancestry, they recommend screening for Tay-Sachs disease. However, many people may not know their ancestry or may not report their ancestry to their healthcare providers.&nbsp;



This new study, published in the journal <a href="https://www.gimopen.org/article/S2949-7744(24)01015-X/fulltext">Genetics in Medicine Open</a>, found that more than half of the carriers of these conditions, 54.9 percent, did not report Jewish or Ashkenazi Jewish ancestry. In other words, they either do not know or do not report having Ashkenazi Jewish ancestry, which is one of the criteria for ACOG ethnicity-based screening guidelines. About half of all carriers had less than 20 percent Ashkenazi Jewish genetic ancestry. This underscores the inadequacy of relying solely on self-reported ethnicity or genetic ancestry for carrier status screening.



“Our research suggests that many individuals who are carriers for one of these inherited conditions are being missed under current ethnicity-based screening criteria,” said Dr. Noura Abul-Husn, VP of Genomic Health at 23andMe and senior author of the study.&nbsp;



<h2 class="wp-block-heading" id="h-criteria-misses-many-at-risk">Criteria Misses Many at Risk </h2>



Carrier screening has long been a crucial tool for identifying genetic conditions inherited in an autosomal recessive or X-linked manner. Some of these inherited conditions are also much more common in some ethnicities than others. 



It’s estimated that about one in three people of Ashkenazi ancestry are carriers for 16 genetic disorders more common in that population. For many years, screening recommendations from the ACOG and others have suggested that people of Ashkenazi descent be screened for many of these conditions.



For this study, 23andMe researchers analyzed the self-reported ethnicity and genetic ancestry of over 7.2 million 23andMe customers who consented to participate in the research. The scientists then identified 116,517 individuals who were carriers of inherited conditions for which ACOG recommends carrier screening in the Ashkenazi Jewish population.



More than half of those carriers, 54.9 percent, did not report Jewish ethnicity, which is one of the ACOG ethnicity-based screening guidelines criteria.



<h2 class="wp-block-heading" id="h-moving-beyond-ethnicity-based-screening">Moving Beyond Ethnicity-Based Screening</h2>



These findings have profound implications. This work is consistent with previous research that has demonstrated that ethnicity-based carrier screening can result in the under-detection of carriers. 



Another medical society, the American College of Medical Genetics and Genomics (ACMG), issued guidelines in 2021 recommending that healthcare providers not use ethnicity to guide carrier screening. Instead, the ACMG recommended screening everyone using the same tiered approach. However, some insurance companies do not provide coverage for this type of carrier screening. Those insurers cite ACOG ethnicity-based carrier screening as a justification.&nbsp;



Knowing carrier status allows prospective parents to make informed decisions regarding family planning, like pursuing in vitro fertilization with genetic screening or preparing for the birth of a child with a genetic condition. Moving beyond ethnicity-based carrier screenings, we can improve the detection of carriers and better assess reproductive risks, ultimately leading to more informed and effective healthcare decisions.



This research calls for reevaluating current guidelines and shifting towards more inclusive and comprehensive genetic screening approaches that do not rely on self-reported ethnicity.



<h2 class="wp-block-heading" id="h-learn-more">Learn More</h2>



<a href="https://www.23andme.com/dna-health-ancestry/">23andMe&#8217;s Health &amp; Ancestry Service</a> includes reports on more than 45 inherited conditions, including cystic fibrosis, sickle cell anemia, and Tay-Sachs disease. 



Find out more about all that 23andMe has to offer <a href="https://www.23andme.com/compare-dna-tests/">here</a>.

The Shortcomings of Ethnicity-Based Carrier Screening

In early July, President Biden signed into law the<a href="https://www.instagram.com/p/C88OKGZNQwn/?igsh=MTc4MmM1YmI2Ng%3D%3D"> National Plan to End Parkinson&#8217;s Act</a>. This is a monumental step forward for the scientists at 23andMe and the millions living with Parkinson&#8217;s disease. Seeing this bipartisan legislation become law is heartening, as it will bolster efforts to find new treatments and ultimately cure Parkinson&#8217;s.



<figure class="wp-block-image alignright size-medium"><img loading="lazy" decoding="async" width="282" height="300" src="http://35.88.189.111/wp-content/uploads/2022/03/PD-Research-282x300.png" alt="" class="wp-image-29642" srcset="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, https://blogcms.23andme.com/wp-content/uploads/2022/03/PD-Research.png 861w" sizes="auto, (max-width: 282px) 100vw, 282px" /></figure>



23andMe launched its <a href="https://www.23andme.com/pd/">Parkinson&#8217;s Research</a> effort 15 years ago, leveraging its unique research model to aid in the fight against this disease. For many of us, this research is personal—we have family members or loved ones living with Parkinson&#8217;s. Along with our ongoing research, 23andMe was the first direct-to-consumer genetic testing company to offer reports authorized by the FDA that estimated a person’s genetic likelihood of developing Parkinson’s disease.



We’ve continued that commitment to our customers and toward <a href="https://blog.23andme.com/articles/preliminary-results-from-the-parkinsons-impact-project-baseline-survey">important Parkinson’s research.</a> More than 37,000 people with Parkinson&#8217;s are part of our Parkinson&#8217;s Research community. That community and the millions of 23andMe customers who have consented to participate in our research make this work possible. Together, we&#8217;ve published over two dozen papers. Collaborating with the Michael J. Fox Foundation (MJFF) and the Parkinson&#8217;s Foundation, we are getting closer daily to our goal of ending Parkinson&#8217;s.



Modeled after the National Alzheimer&#8217;s Project Act (NAPA) of 2011, the new law will direct more attention and funding toward Parkinson&#8217;s research, just as NAPA did for Alzheimer&#8217;s. In the last year, two new treatments have been approved by the FDA to treat early Alzheimer&#8217;s, and there are now some new tests that help with earlier diagnosis of the disease. The hope is that the National Plan to End Parkinson&#8217;s Act will lead to similar breakthroughs for treating and diagnosing Parkinson&#8217;s disease.



We talked to a few of the 23andMe scientists working on Parkinson&#8217;s research to get their reaction to the new law and what it may mean for new treatments for Parkinson&#8217;s disease.



<h2 class="wp-block-heading" id="h-promising-new-research">Promising New Research</h2>



Hopefully, this new law will spur additional funding for Parkinson&#8217;s research. Looking at all the Parkinson&#8217;s research, including work by 23andMe researchers on topics such as<a href="https://academic.oup.com/brain/article/147/6/1996/7676517?login=false"> LRRK2 G2019S</a>, the<a href="https://blog.23andme.com/articles/parkinsons-disease-and-the-microbiome"> microbiome, and Parkinson&#8217;s</a> and <a href="https://blog.23andme.com/articles/large-study-on-parkinsons-disease-includes-understudied-populations">Parkinson&#8217;s in non-European populations</a>, what are you most excited about in current Parkinson&#8217;s research?



<figure class="wp-block-image alignright size-medium"><img loading="lazy" decoding="async" width="300" height="228" src="http://35.88.189.111/wp-content/uploads/2024/05/Mapping-LRRK2-Symptoms-to-Brain-300x228.png" alt="Mapping of LRRK2 PD symptoms to areas of the brain." class="wp-image-32942" srcset="https://blogcms.23andme.com/wp-content/uploads/2024/05/Mapping-LRRK2-Symptoms-to-Brain-300x228.png 300w, https://blogcms.23andme.com/wp-content/uploads/2024/05/Mapping-LRRK2-Symptoms-to-Brain-768x584.png 768w, https://blogcms.23andme.com/wp-content/uploads/2024/05/Mapping-LRRK2-Symptoms-to-Brain-1024x779.png 1024w, https://blogcms.23andme.com/wp-content/uploads/2024/05/Mapping-LRRK2-Symptoms-to-Brain-880x670.png 880w, https://blogcms.23andme.com/wp-content/uploads/2024/05/Mapping-LRRK2-Symptoms-to-Brain-1180x898.png 1180w, https://blogcms.23andme.com/wp-content/uploads/2024/05/Mapping-LRRK2-Symptoms-to-Brain.png 1899w" sizes="auto, (max-width: 300px) 100vw, 300px" /></figure>



23andMe PD Research Team: The Parkinson’s research landscape is expanding into so many promising areas that choosing just one is difficult! A few of our top research priorities at this time include exploring Parkinson’s genetic insights into multi-ancestry populations, early Parkinson’s disease detection, and the importance of gut/saliva microbes. Scientists are developing accessible assays of alpha-synuclein—the protein that misfolds and is associated with the development of Parkinson’s—that will aid in early detection and spur further insights into disease progression. There is still so much work to do, and we are excited to contribute research in genetics, ancestry, and the microbiome to understand Parkinson’s biology and pathology further.



<h2 class="wp-block-heading" id="h-the-alzheimer-s-research-example">The Alzheimer&#8217;s Research Example</h2>



The new law was modeled after the National Alzheimer&#8217;s Project Act. What do you see as a parallel with Alzheimer&#8217;s research, and where does the comparison diverge?



23andMe PD Research Team: Both Alzheimer’s and Parkinson’s are neurodegenerative diseases that pose real challenges to the patients living with them, as well as to the researchers trying to find a breakthrough. Both diseases currently have treatments that primarily address symptoms rather than cure the disease, so both camps of researchers are actively looking for a breakthrough. The etiologic and clinical details can be different—for example, PD often begins with motor symptoms while AD’s early manifestations are more cognitive—but the commonalities in studying the two conditions are much more pronounced.



<h2 class="wp-block-heading" id="h-23andme-s-parkinson-research">23andMe&#8217;s Parkinson Research</h2>



23andMe has been studying Parkinson&#8217;s disease since 2009, and our findings have been published in more than two dozen papers. Is there a big takeaway from all that work and the ongoing work on Parkinson&#8217;s?



<figure class="wp-block-image alignright size-full"><img loading="lazy" decoding="async" width="332" height="332" src="http://35.88.189.111/wp-content/uploads/2019/02/BHM-Microscope-NoBack.png" alt="" class="wp-image-26906" srcset="https://blogcms.23andme.com/wp-content/uploads/2019/02/BHM-Microscope-NoBack.png 332w, https://blogcms.23andme.com/wp-content/uploads/2019/02/BHM-Microscope-NoBack-150x150.png 150w, https://blogcms.23andme.com/wp-content/uploads/2019/02/BHM-Microscope-NoBack-300x300.png 300w, https://blogcms.23andme.com/wp-content/uploads/2019/02/BHM-Microscope-NoBack-271x271.png 271w" sizes="auto, (max-width: 332px) 100vw, 332px" /></figure>



23andMe PD Research Team: Before the 21st century, genetics were thought to have little to no influence on Parkinson’s disease. Thanks to the advent of sequencing technologies, we have learned a great deal about the genetic underpinnings of Parkinson’s. 23andMe has been an essential contributor to Parkinson’s genetics research due to our unique and large customer base that is highly engaged in research. The big takeaway from our science has been the identification of ~90 genes that are associated with the risk of Parkinson’s. With each decade that passes, we are learning more and more about how genetics influences Parkinson’s disease risk and symptoms. This knowledge is the foundation used to develop genetic testing and improve early detection of Parkinson’s disease, identify new drug targets, and develop new medications.



<h2 class="wp-block-heading" id="h-collaborations">Collaborations</h2>



For almost our entire Parkinson&#8217;s research program, 23andMe has collaborated with the Michael J. Fox Foundation and the Parkinson&#8217;s Foundation. We&#8217;ve also collaborated with some academic institutions and the NIH. Where are we most interested in collaborating on areas around Parkinson&#8217;s disease? Will we likely see access to this dataset expanded to more qualified researchers?



23andMe PD Research Team: Scientific collaboration is crucial to succeed in Parkinson’s research. We are interested in continuing our support and collaboration with ongoing studies, including The Michael J. Fox Foundation’s PPMI and The University of Rochester’s VALOR-PD studies. We are excited to contribute to Radboud University Medical Center’s Slow-SPEED study—the first-ever remote exercise intervention in prodromal Parkinson’s. We are also excited to explore the capabilities of wearable devices in detecting early Parkinson’s and cognitive games to monitor brain health over time. The 23andMe Research Team is committed to supporting researchers while protecting the privacy of our customers and research participants.



<h2 class="wp-block-heading" id="h-lrrk2-study">LRRK2 Study</h2>



Recently, 23andMe published findings focusing on those with the <a href="https://academic.oup.com/brain/article/147/6/1996/7676517?login=false">LRRK2 variant and Parkinson&#8217;s.</a> The study highlights how the disease affects people differently. What more can you say about LRRK2 and how the disease doesn&#8217;t necessarily affect all people similarly?



23andMe PD Research Team: We showed that the LRRK2 G2019S variant increases one’s risk of Parkinson’s. However, not everyone with the mutation will develop Parkinson’s. Furthermore, we saw that this increased risk was partly explained by other genes. The cumulative effect of these other genes, called a polygenic risk score, further explained this variability in Parkinson’s risk in LRRK2 G2019S carriers. Therefore, LRRK2 can affect people differently, and this has to do with both our background genetic makeup and our environment.



<h2 class="wp-block-heading" id="h-research-participants">Research Participants</h2>



All our work is possible because people with Parkinson&#8217;s have chosen to participate in this research. We also have about 12 million customers who&#8217;ve consented to participate in research. What would you like to say to those people with Parkinson&#8217;s who are research participants? What about those who do not have Parkinson&#8217;s? How is their participation helpful for what you do?



23andMe PD Research Team: We want to thank all of our customers for taking the time to participate in 23andMe research. Without you, progress in Parkinson’s research would not be possible. Genetic analyses require thousands of research participants to glean robust insights. We&#8217;re grateful to have such an engaged customer base committed to research. We want everyone to access, understand, and benefit from the human genome. This all starts with research.



<h2 class="wp-block-heading" id="h-motivation">Motivation</h2>



Many of us here at 23andMe have family members who are living with or lived with Parkinson&#8217;s disease. Does that help motivate you to do the research you are doing?



23andMe PD Research Team: Absolutely. One of our core values is ‘behind every data point is a human being.’ That comes naturally when so many of us have personal connections to PD. Research in service of better quality of life and treatment options for people just like our loved ones is our North Star.



<h2 class="wp-block-heading" id="h-the-value-of-knowing">The Value of Knowing</h2>



We also know 23andMe customers are interested in their Genetic Health Risk report on Parkinson’s Disease. Not everyone wants to learn this information. However for those who do, what do you see as the value of learning that you may have a genetic risk for Parkinson’s disease?&nbsp;



23andMe PD Research Team: The benefits for those who learn about their genetic risk can be tangible. Knowing genetic risk can lead to more proactive health monitoring and early detection. Also, individuals with a known genetic predisposition to PD may consider genetic counseling to understand the implications for their children and other family members. Finally, some individuals find value in being mentally and emotionally prepared for the possibility of developing Parkinson’s disease.

A New Era for Parkinson’s Research

This week, 23andMe and 20 nonprofits, advocacy groups, and research institutions launched a new Lung Cancer Genetics Study. This study unites patients, advocates, doctors, and scientists to transform our understanding of the genetics of lung cancer with the hope of advancing research toward finding a cure.



<figure class="wp-block-image alignright size-medium"><img loading="lazy" decoding="async" width="240" height="300" src="http://35.88.189.111/wp-content/uploads/2024/07/NSCLC_960x1200-1-240x300.jpg" alt="" class="wp-image-33185" srcset="https://blogcms.23andme.com/wp-content/uploads/2024/07/NSCLC_960x1200-1-240x300.jpg 240w, https://blogcms.23andme.com/wp-content/uploads/2024/07/NSCLC_960x1200-1-768x960.jpg 768w, https://blogcms.23andme.com/wp-content/uploads/2024/07/NSCLC_960x1200-1-819x1024.jpg 819w, https://blogcms.23andme.com/wp-content/uploads/2024/07/NSCLC_960x1200-1-704x880.jpg 704w, https://blogcms.23andme.com/wp-content/uploads/2024/07/NSCLC_960x1200-1-944x1180.jpg 944w, https://blogcms.23andme.com/wp-content/uploads/2024/07/NSCLC_960x1200-1.jpg 1920w" sizes="auto, (max-width: 240px) 100vw, 240px" /></figure>



Through this collaborative study, we aim to recruit 10,000 people diagnosed with lung cancer to participate in this crucial research that could help others in the future.



<h2 class="wp-block-heading" id="h-a-broad-collaboration">A Broad Collaboration</h2>



Those who participate will help 23andMe and collaborating organizations create a repository of genetic and other data for lung cancer research by qualified scientists. This research data could be used to better identify those at the highest risk for lung cancer and discern how genetic and lifestyle factors play a role. The study could also improve earlier detection through enhanced screening. In addition, the research could also be used to develop more personalized treatments, as genetic research can help inform more targeted therapies.



Together, we&#8217;ll learn more about the genetic factors that impact lung cancer and better identify those at the most significant risk. Ultimately, we want to advance research towards finding a cure.



“The link between genetics and lung cancer can transform our understanding of risk and treatment,” said Jill Feldman, a co-founder of the patient advocacy group<a href="https://egfrcancer.org/our-mission/"> EGFR Resisters</a>, a community of people diagnosed with and/or personally affected by EGFR-positive lung cancer.



Jill said seeing such a broad collaboration of groups supporting this study is heartening.



“For the first time, the entire lung cancer community—patients, advocates, doctors, researchers—unites to support this vital study,” said Jill.



Todd Fielder, who is active with the patient advocacy group RET Positive and is a stage 4 lung cancer patient, said the broad coalition supporting this study is motivating.



&#8220;I want to participate in research to help move science forward, to hopefully come up with new treatment options,” said Todd. “If not for myself, then for future generations.&#8221;



<h2 class="wp-block-heading" id="h-about-lung-cancer">About Lung Cancer</h2>



Lung cancer is the number one cause of cancer deaths in both men and women in the United States. In 2020, more people died from lung cancer than breast, colorectal, and prostate cancer combined, according to the<a href="https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2023/2023-cancer-facts-and-figures.pdf"> American Cancer Society Cancer Facts &amp; Figures 2023 report</a>. About one in 16 men and one in 17 women in the United States will be diagnosed with lung cancer in their lifetime, the report indicates. It is the <a href="https://www.cdc.gov/lung-cancer/statistics/">third most common form of cancer</a> in the United States, according to the Centers for Disease Control (CDC). Despite being the deadliest cancer, <a href="https://meetings.asco.org/abstracts-presentations/209631">lung cancer research is underfunded</a> compared to other cancer types. Lung cancer receives $10,000 per death in federal and non-profit cancer funding, whereas breast cancer receives $91,000 per death.



Lung cancer usually begins in the lungs as either a small cell or non-small cell cancer. These two forms grow differently and are treated differently. Although it first starts in the lungs, the cancer may spread to lymph nodes or other areas of the body, such as the brain. When a cancer spreads from one part of the body to another, it’s called metastasis.



<figure class="wp-block-image alignright size-medium"><img loading="lazy" decoding="async" width="300" height="290" src="http://35.88.189.111/wp-content/uploads/2024/07/Lung-Cancer-Enwas-300x290.png" alt="" class="wp-image-33188" srcset="https://blogcms.23andme.com/wp-content/uploads/2024/07/Lung-Cancer-Enwas-300x290.png 300w, https://blogcms.23andme.com/wp-content/uploads/2024/07/Lung-Cancer-Enwas-768x743.png 768w, https://blogcms.23andme.com/wp-content/uploads/2024/07/Lung-Cancer-Enwas-1024x990.png 1024w, https://blogcms.23andme.com/wp-content/uploads/2024/07/Lung-Cancer-Enwas-880x851.png 880w, https://blogcms.23andme.com/wp-content/uploads/2024/07/Lung-Cancer-Enwas.png 1156w" sizes="auto, (max-width: 300px) 100vw, 300px" /></figure>



While most of us know that smoking increases one’s risk, between 10–20 percent of people who develop lung cancers have never smoked or smoked less than 100 cigarettes in their lifetime. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11014425/">Two-thirds</a> of these people are women. Researchers at Harvard made an interesting finding among lung cancer patients who never smoked. Still, they had a family history of lung cancer, pointing to a specific genetic mutation in the epidermal growth factor receptor gene, EGFR. Published in the scientific journal <a href="https://pubmed.ncbi.nlm.nih.gov/16258541/">Nature Genetics</a>, the study found that an EGFR mutation that is present in many patients&#8217; tumors increases the risk of developing lung cancer when it is inherited genetically. It has been estimated that this EGFR T790M mutation is a major cancer predisposition gene, with carriers having an estimated <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4509739/">31% risk of developing lung cancer.</a>



In fact, there are many factors, both genetic and non-genetic, that can contribute to lung cancer risk that are not related to smoking. Environmental exposures, other health conditions, lifestyle, and genetics can all play a role. Internal 23andMe data found that a family history of lung cancer, along with different types of allergies or rhinitis, the stuffed or dripping nose caused by allergies, were all associated with lung cancer, but that association does not mean that they were causal.



<h2 class="wp-block-heading" id="h-environmental-factors-in-lung-cancer-risk">Environmental Factors in Lung Cancer Risk</h2>



Air pollution also contributes to the development of lung cancer. One study published in the academic journal <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7614604/#SD1">Nature</a> found that higher rates of air pollution known as PM2.5 are associated with higher rates of lung cancer with mutations in the EGFR gene. The researchers also showed that air pollution may contribute to lung cancer development by helping push lung cells with cancer-causing EGFR mutations over the edge from precancerous to cancerous. Cases of lung cancer are unevenly distributed throughout the United States, with much of the difference between states attributed to factors such as tobacco addiction. Interestingly, however, many areas with higher lung cancer rates also have <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa1702747">high levels of PM2.5 air pollution</a>, underscoring the complex relationship between our health and lifestyle factors, socioeconomic factors, and environmental exposures.



<figure class="wp-block-image aligncenter size-full is-resized"><img loading="lazy" decoding="async" width="512" height="317" src="http://35.88.189.111/wp-content/uploads/2024/07/Lung-Cancer-Rate-by-State.png" alt="" class="wp-image-33187" style="width:512px;height:auto" srcset="https://blogcms.23andme.com/wp-content/uploads/2024/07/Lung-Cancer-Rate-by-State.png 512w, https://blogcms.23andme.com/wp-content/uploads/2024/07/Lung-Cancer-Rate-by-State-300x186.png 300w" sizes="auto, (max-width: 512px) 100vw, 512px" /></figure>



State by State Cancer rate per 100,000 people. Source: U.S. Cancer Statistics Working Group. https://www.cdc.gov/cancer/dataviz, released in June 2024.



While the genetics of lung cancer are not yet well understood, it’s estimated that <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10681406/">up to 15% of people</a> diagnosed with lung cancer may have DNA variants linked to cancer development. One study of 5000 people diagnosed with lung cancer in Utah found that those with a family history of lung cancer in their immediate family (like parents, siblings, or children) <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6592768/">were more than twice as likely</a> to be diagnosed with lung cancer as people with no family history. The risk generally increased with the number of diagnosed family members. Even individuals with only second or third-degree relatives affected by lung cancer were at higher risk. (Second-degree relatives include family members like grandparents, aunts, uncles, nieces, nephews, and half-siblings; third-degree relatives include family members like great-grandparents, great-aunts, great-uncles, and first cousins.)&nbsp;



Understanding more about the role that both the environment and genetics play in lung cancer will help scientists work to develop new and more personalized therapies. This is particularly true for people who develop lung cancer at an early age or who don’t have known risk factors such as smoking history or <a href="https://www.epa.gov/radon/health-risk-radon#iowa">radon exposure</a>, which is another known cause of lung cancer.



<h2 class="wp-block-heading" id="h-more-about-the-lung-cancer-genetics-study">More about the Lung Cancer Genetics Study</h2>



Like all 23andMe research, a research ethics committee will oversee the Lung Cancer Genetics Study. In the United States, this is called an Institutional Review Board (IRB), which is an independent ethics panel that ensures research is conducted in accordance with government and ethical guidelines.



23andMe’s unique research platform — its ability to enroll participants online — makes it ideal for this study. The de-identified data from this study will be made available to approved researchers and to approved nonprofit researchers and institutions at no cost. Along with de-identified genetic data, the scientific database will include data from surveys on participants&#8217; lung cancer experience and, in some cases, data from medical records and tumor testing.



The Lung Cancer Genetics Study is made possible by Troper Wojcicki Philanthropies.



To learn more about the study, our collaborators, and eligibility criteria, visit the <a href="https://enroll.23andme.com/research/lung-cancer/identity/">Lung Cancer Genetics Study landing page</a>.

An image of 23andMe's Lung Cancer Study logo

23andMe Collaborates on New Genetic Study of Lung Cancer

People love coffee, which is partially explained by genetics, but you’d be forgiven for being less sure if your daily cup of joe is good for you.



Researchers have been wrestling with that question for years, studying the genetics associated with coffee consumption.



<h2 class="wp-block-heading" id="h-wired">Wired</h2>



People are <a href="https://blog.23andme.com/articles/coffee-tea-and-23andme">genetically wired </a>to react differently to their morning coffee. Your genetics affect how you metabolize caffeine and your bitter taste perception, and both are associated with how much coffee you consume. Genetic differences can explain why some people can chug a Venti without problem, while a few sips are enough to perk up someone else all day long.



There are health implications for all this, but those are less clear-cut, and the data cuts both ways.



A recent study led by researchers at UC San Diego and Western University in Ontario, Canada, illustrates how complicated it is to understand the health outcomes of coffee consumption. The study found clear genetic associations with drinking coffee, but the same study found conflicting data around health outcomes. However, those divergent findings may say more about differences in culture or coffee culture than anything else.



<h2 class="wp-block-heading" id="h-health-outcomes">Health Outcomes</h2>



The study, published in the journal<a href="https://doi.org/10.1038/s41386-024-01870-x"> Neuropsychopharmacology</a>, used data from two sources: a cohort of about 330,000 people in the UK Biobank and another data set from about 130,000 23andMe customers who consented to participate in research.



“We used this data to identify regions on the genome associated with whether somebody is more or less likely to consume coffee, and then identify the genes and biology that could underlie coffee intake,” said Hayley Thorpe, the lead researcher on the study and a postdoctoral researcher at Western’s Schulich Medicine &amp; Dentistry.



The data confirmed seven previously known genetic associations with coffee consumption. Some shared health outcomes were also found in both cohorts, but what was striking was where the health outcome data diverged. More than 80 percent of the outcomes were positive within the 23andMe data set, whereas only about 54 percent of the health outcomes were positive within the UK Biobank data set.



<h2 class="wp-block-heading" id="h-coffee-culture">Coffee Culture</h2>



Pierre Fontanillas, a senior scientist of statistical genetics at 23andMe and one of the study&#8217;s lead researchers, said the stark differences in the health outcomes in the two datasets may be more related to the differences in the coffee culture between the UK and the United States.



“Your genetics influences your coffee consumption, but there are other factors, like culture and environment,” Pierre said.&nbsp;&nbsp;



Although the research participants from the UK Biobank and 23andMe have a lot in common, there are differences between the two groups that highlight just how complicated this kind of research can be. For instance, in the United States, serving sizes tend to be larger than in the UK. In addition, people in the US are more likely to add sweeteners or frothed milk to their coffee drinks, and they are more likely to augment their caffeine consumption with caffeinated sodas. Instant coffee is more common in the UK, serving sizes are small, and coffee drinkers may also increase their caffeine consumption with tea.



“That could explain some of those differences,” Pierre said.



While there were differences in health outcomes, health outcomes were also shared within both cohorts. Both showed genetic associations between coffee and harmful health outcomes such as obesity and substance use, for instance.



However, the two cohorts diverged when looking at other health and psychiatric traits.



“Look at the genetics of anxiety, for instance, or bipolar and depression,” said Thorpe at Western University. “In the 23andMe data set, they tend to be positively genetically correlated with coffee intake genetics. But then, in the UK Biobank, you see the opposite pattern, where they’re negatively genetically correlated. This is not what we expected.”



<h2 class="wp-block-heading" id="h-learn-more">Learn More</h2>



23andMe’s<a href="https://www.23andme.com/dna-health-ancestry/"> Health + Ancestry Service</a> can help you learn about genetic factors that may be involved. Order a kit, send us your spit, and find out what your genetics <a href="https://blog.23andme.com/articles/happy-international-coffee-day">predict about your caffeine consumption </a>level.

Research — Page 5