By Eli Chanoff, 23andMe Research Associate
Parkinson’s disease (PD) has been a central focus of 23andMe’s research since our company’s early years. Over more than a decade, we have grown a community of tens of thousands of individuals, with and without Parkinson’s, who are committed to making a difference through research. Together with this community, 23andMe researchers have contributed to more than 20 papers offering new insights into the disease. As a result, we are in a unique position to advance our understanding of this disease, and in particular to investigate the role that genetics play in both Parkinson’s disease risk and progression.
The G2019S variant in the LRRK2 gene is associated with a significantly increased risk of developing Parkinson’s disease. 23andMe launched the Parkinson’s Impact Project (PIP) in 2018 with the aim of learning about the experience of people who carry the LRRK2 G2019S variant. The project consists of a comprehensive baseline survey as well as shorter quarterly follow-up sessions completed by consented research participants who are eligible carriers with and without a diagnosis of PD. The baseline survey is also completed by a large group of consented, eligible research participants without the G2019S variant who were matched to the carriers based on age and sex.
Less than half of individuals with one copy of the variant develop Parkinson’s disease. Understanding why some carriers develop the disease while others don’t could offer key insights into novel approaches to slowing or stopping disease progression.
In addition, since a higher portion of the carrier population is at risk of being diagnosed with PD, it’s safe to assume that the cohort will also have an increased proportion of individuals with early-stage (prodromal) disease, but who have not yet been diagnosed. Therefore, traits that are enriched in the carrier cohort relative to matched controls may represent early warning signs of Parkinson’s disease. However, these traits could also be a consequence of the G2019S mutation that is entirely unrelated to PD. Follow-up analyses are needed to distinguish between findings that are due to simply being a LRRK2 G2019S carrier and those that are due to having early-stage disease.
Although this is very much a work in progress, we strongly believe it is important and appropriate for us to share preliminary data with those participating in the study as well as the broader community. Below we review a few of our initial results from the analysis of the baseline survey data.
Of those surveyed, 16 percent of G2019S carriers and 2.6 percent of non-carriers reported a diagnosis of Parkinson’s disease. We have separated our cases and controls into those with and without the G2019S variant–regardless of Parkinson’s status–so as to specifically measure the association between this genetic variant and a set of Parkinson’s-related phenotypes.
In this context, phenotypes can refer to traits, clinical symptoms, environmental exposures, and comorbidities. When considering the link between any phenotype and Parkinson’s, it is important to remember that a phenotype could be caused by PD, could be a risk factor for PD, or could be an early warning sign of PD. Symptoms are a subset of phenotypes and are distinct from other phenotypes–even physiological ones–because of their use in a clinical setting.
Below you will find some of the data we gathered from the PIP baseline survey. Please note that presenting with any of these phenotypes does not mean that you have Parkinson’s disease. Our services are not meant to diagnose or treat any disease. Please contact your doctor or a movement disorder specialist if you want to be evaluated for Parkinson’s.
Motor symptoms, such as tremors, stiff or slow movements, impaired posture or balance, and rigidity, are the characteristics most commonly used to diagnose Parkinson’s disease. While other motor and non-motor phenotypes are also common, these canonical motor symptoms remain more widely studied and are often what first comes to mind when people think about PD.
The baseline survey asked respondents about a series of motor phenotypes derived from the commonly used MDS-UPDRS rating scale, a few of which are included below. This chart shows the percentage of G2019S carriers and non-carriers who reported experiencing trembling or shaking in any part of their body, changes in handwriting, changes in gait, or stooping posture. Recall that both carriers and non-carriers may or may not have a diagnosis of Parkinson’s disease.
These data show that some motor phenotypes previously associated with non-genetic Parkinson’s disease, were reported more frequently by G2019S carriers than non-carriers. While more analysis is needed, early results support the hypothesis that carriers are at increased risk of experiencing these symptoms based on their genetics.
In addition to motor symptoms, several non-motor phenotypes have been linked to Parkinson’s disease. However, many of these such as constipation and cognitive changes also occur in non-PD populations and like PD also increase in frequency with age, making the selection of appropriate controls very important.
In the first chart below, we show results from our survey for a few non-motor PD phenotypes. This chart shows the percentage of carriers and non-carriers who reported having trouble concentrating on things, like reading the newspaper or watching television, or who felt down, depressed, or hopeless on at least half of the days in the previous two weeks. It also includes those who reported having fewer than three bowel movements in a typical week.
These data do not show a clear difference between carriers and non-carriers for their risk of developing certain non-motor phenotypes.
Our survey also asks for additional pieces of participants’ health histories so as to assess possible links between other health conditions and Parkinson’s disease. Finding an association between PD and another condition may suggest that there are similarities between the biological pathways underlying either disease. Beyond that, establishing these associations also helps us understand the significance of different PD risk factors.
In this second chart, we show results for a few conditions that are thought to have some relationship with PD. It shows the percentage of carriers and non-carriers who have been diagnosed with or treated for restless leg syndrome, head injury or concussion, and allergies.
Interestingly, these data suggest that having the LRRK2 G2019S variant may increase the risk of having allergies. A previous 23andMe publication titled The Parkinson’s phenome–traits associated with Parkinson’s disease in a broadly phenotyped cohort found a link between seasonal allergies and PD, suggesting a possible similarity in the immune system’s role in both conditions. Our new results support that possibility.
The data provided by the respondents to this survey serve as an important first step toward measuring disease progression and potentially identifying clinically useful early signs of PD in LRRK2 G2019S carriers. By participating in our surveys, 23andMe customers are filling in the gaps in our knowledge, and providing a clearer picture of how this disease manifests.
We are excited to continue this research, and we are grateful for the many consented research participants who make this research possible. We aim to share results from the Parkinson’s Impact Project as our collection of phenotypic data grows.