This week, researchers with the National Institutes of Health, in collaboration with 23andMe and about a dozen other groups, published the largest to-date genetic study of Parkinson’s disease. Notably, it is the first large-scale genetics study of Parkinson’s disease to include data from individuals from multiple ancestral populations.
Published in the journal Nature Genetics, the study identified a dozen genetic loci not previously known to be associated with Parkinson’s. In addition, it confirmed 66 other known loci associated with this incurable neurodegenerative disease. It also found that some variants were associated with risk across all the populations studied.
The Importance of Diversity in Research
This study is a reminder of the need to include more diverse populations in research, and it also highlights the potential for 23andMe to do just that. The study identified four novel gene regions associated with Parkinson’s that have different effects on different populations — in this case, people of European, East Asian, Latin American, and African ancestry.
However, even though this was a multi-ancestry study, there was far more data from people of European ancestry. In addition, the smaller numbers of people from non-European populations in the study meant that some of the ancestry-specific findings failed to reach statistical significance. According to the researchers, this highlights the need for more data from non-European populations to fully power this kind of research.
By including diverse populations in research, it ensures that scientists can identify population-specific genetic variations that may play a role in a disease like Parkinson’s. There is currently no other study cohort with the scale and diversity of 23andMe, which has millions of participants from diverse backgrounds who are both engaged and consented to participate in a wide variety of genetic research. However, even with the diversity of its dataset, 23andMe continues to focus on encouraging more people of non-European ancestry to participate not just in our research but the research of our collaborators.
23andMe Parkinson’s Research
The study is one of many different projects 23andMe has engaged in since launching its Parkinson’s disease research program in 2009.
Just this week, in another collaboration between 23andMe and the NIH, researchers published a study analyzing about 1,000 rare variants previously associated with Parkinson’s disease. Published in the journal Nature, the paper included data from more than three million people that included about 30,000 individuals with Parkinson’s. The study was noteworthy not so much for identifying rare variants but for determining that many of these variants previously identified as associated with the disease may not in fact play a role in Parkinson’s afterall. The study did however confirm the strong association between variants in the LRR2 and GBA1 genes and Parkinson’s.
23andMe scientists study many conditions and traits, but research into Parkinson’s disease is particularly important because of our long-term commitment to studying this condition, which affects about a million people in the United States alone.
Parkinson’s is the second most common neurodegenerative condition behind Alzheimer’s disease. Parkinson’s disease leads to a loss of nerve cells in the part of the brain that controls movement. As a result, there are a range of symptoms among those with the condition, and it also progresses differently within people. Symptoms include motor problems, such as tremors, stiffness of the muscles, and slow movements, as well as non-motor symptoms, such as problems with low blood pressure on standing, constipation, or sleep disturbances.
Our Parkinson’s disease research was one of the first disease-specific “deep dive” research projects 23andMe undertook, and it offered a model for other disease research. In the last 14 years, our Parkinson’s research efforts have reached several milestones, and that wouldn’t have been possible without our research participants or the vital assistance of our collaborators at The Michael J. Fox Foundation.
We currently have more than 30,000 people with Parkinson’s disease who have consented to participate in our Parkinson’s research, and another 500,000 people without Parkinson’s disease who are also participating in our research efforts. Those participants have helped 23andMe scientists and our collaborators complete work leading to 30 published papers, including ten since 2020 alone. These studies have also identified almost 100 new genetic variants associated with Parkinson’s disease.
Learning from LRRK2
23andMe researchers are currently studying non-genetic traits that may help in diagnosing Parkinson’s disease earlier, as well as identifying putative causal risk factors that influence the age of onset of the illness.
Our scientists are also learning more about how to characterize different types of Parkinson’s; for example, we are currently studying the LRRK2 G2019S founder mutation, which is the most common cause of “genetic” Parkinson’s. Our LRRK2 cohort is three times the size of the next largest research cohort of people with this condition. Known as the Parkinson’s Impact Project, or PIP, our researchers are learning a lot from this study.
For example, people with this LRRK2 variant tend to see a slower disease progression with fewer non-motor symptoms. They’re also much more likely to be of Ashkenazi Jewish descent, which relates to the history of the LRRK2 G2019S founder mutation history. It is thought to have originated from a Berber founder from North Africa more than 5,000 years ago, and later flowed into the Jewish community that eventually migrated into central Europe.
This study also highlights another aspect of our research. Differences in the symptoms suggest that different map areas of the brain may be less affected in LRRK2 Parkinson’s disease. This will help researchers distinguish the various subtypes of Parkinson’s disease.
For instance, individuals with the LRRK2 variant have lower rates of REM sleep behavior disorder, or RBD. This symptom includes acting out of dreams during sleep. RBD is much more common in people with idiopathic Parkinson’s disease, or Parkinson’s that is caused by some unknown cause rather than by genetics. Loss of smell is also a symptom of Parkinson’s disease, but people with LRRK2 G2019S have lower rates of loss of smell. In addition, people with LRRK2-associated Parkinson’s have fewer cognition issues.
Data like this helps inform scientists about the disease and its progression, and can inform the prognosis. 23andMe scientists are working on ways to better identify people at risk of Parkinson’s and better understand how the disease may manifest and progress in those individuals.
23andMe’s Parkinson’s disease research program is unique in that it allows for continued engagement with participants. Scientists are better able to track changes and understand the progression of Parkinson’s. Having people who are engaged in this research over time also allows our scientists to nimbly add new dimensions to their investigations into this disease.
For example, one of our postdoctoral fellows, Keaton Stagaman, recently completed a small-scale pilot study in collaboration with The Michael J. Fox Foundation, looking at the gut and oral microbiomes of people with Parkinson’s. It turned out to be the largest single study to test the relationship between the oral and gut microbiomes in Parkinson’s disease.
Another common symptom of Parkinson’s is intestinal problems, such as constipation. Over the last few years, much focus has been on the gut-brain connection and its relationship with disease. Our researchers wanted to understand whether the gut microbiome might play a vital role in the pathological onset of Parkinson’s disease. Our researchers are still digging through this data and plan to follow up with a much larger study later this year, including healthy controls.
We will eventually publish our research findings on this study and others, and share that information with our research participants. Finding better early-detection methods may be critical in modifying the impact of this neurodegenerative disease. Earlier intervention could help prevent the loss of neurons and stave off the worsening of symptoms, for instance. Understanding how Parkinson’s disease manifests and progresses among different people is also important.
None of this work would be possible without those individuals — both with Parkinson’s disease and those who do not have it — who’ve consented to participate in 23andMe research.
Learn more about 23andMe’s Parkinson’s disease research here.