Largest study on the LRRK2 variant leads to discoveries about health, ancestry, and history
23andMe, in collaboration with The Michael J. Fox Foundation for Parkinson’s Research, conducted the largest study on the LRRK2 G2019S variant, revealing new insights into Parkinson’s disease. The study, launched in 2018, included 1,286 carriers and 109,154 non-carriers over 3.5 years. Findings indicate that LRRK2 carriers are seven times more likely to develop Parkinson’s but experience milder symptoms and slower disease progression compared to non-carriers. The research also uncovered genetic hotspots in Mexico, Cuba, Puerto Rico, and Brazil, linking them to historical migrations of Jewish populations. Results published in the June 2024 issue of Brain highlight the need for more sensitive early detection criteria for LRRK2 carriers.
- Largest study on LRRK2 G2019S variant involved 1,286 carriers and 109,154 non-carriers.
- People with LRRK2 G2019S are seven times more likely to develop Parkinson’s disease.
- LRRK2-associated Parkinson’s has milder symptoms and slower progression.
- 23andMe identified genetic ‘hotspots’ linked to historical Jewish migration.
- Study revealed novel ancestry connections in Mexico, Cuba, Puerto Rico, and Brazil.
- The research utilized longitudinal data collection over 3.5 years.
- Supported by The Michael J. Fox Foundation, enhancing study credibility.
- 23andMe’s cohort is three times bigger than any other similar study.
- Longitudinal data collection improves understanding of disease progression.
- Ongoing commitment to Parkinson’s research since 2009, identifying almost 100 new genetic variants.
- Only 66% of participants completed at least one follow-up survey.
- Just 42% of participants with Parkinson’s had at least two years of follow-up.
- Risk of Parkinson’s might be underestimated due to current detection criteria focusing on sleep and smell abnormalities.
- Existing criteria may lack sensitivity for early detection among LRRK2 carriers.
Insights
23andMe's study on the LRRK2 G2019S variant has profound implications for our understanding of Parkinson's disease. The discovery that carriers of this variant are seven times more likely to develop Parkinson's disease is a significant finding. This variant's association with milder symptoms and slower disease progression compared to idiopathic Parkinson's provides valuable insights for both patients and researchers. The study also revealed that common early symptoms like REM sleep behavior disorder and loss of smell are less prevalent in LRRK2 variant carriers, suggesting that current diagnostic criteria might miss early detection in these individuals.
From a research perspective, the identification of new genetic hotspots in populations from Mexico, Cuba, Puerto Rico and Brazil expands our understanding of the genetic diversity of Parkinson’s disease. This raises questions about the historical migration and genetic integration in these populations. Furthermore, the study's large cohort size strengthens the validity of these findings, making it a pivotal reference for future research.
For retail investors, understanding that 23andMe is at the forefront of such groundbreaking research enhances the company's credibility and positions it as a leader in genetic health research. This could lead to increased investor interest and potential funding for further research.
The publication of 23andMe's study on the LRRK2 variant in a reputable journal like Brain can positively impact the company's stock performance. The study not only showcases 23andMe's research capabilities but also underscores its commitment to advancing the understanding of Parkinson's disease. This positions the company favorably in the biopharmaceutical sector, potentially attracting partnerships and funding.
The collaboration with The Michael J. Fox Foundation also highlights strong stakeholder engagement, which can boost investor confidence. The foundation's support underscores the study's importance and credibility. Moreover, the detailed longitudinal data collected from a large cohort over 3.5 years provides a robust foundation for future research and potential development of targeted therapies.
However, investors should also be aware of the long-term nature of such research. While the findings are significant, translating these insights into commercial products or treatments will take time. Thus, while the immediate impact on stock prices might be positive, the long-term financial benefits will depend on the successful development and commercialization of new therapies based on these findings.
Findings from 23andMe research on Parkinson’s disease published in Brain
- The LRRK2 variant is strongly associated with symptoms of Parkinson’s disease (PD) that are different from non-variant carriers with the disease
- The study revealed novel findings of genetic “hotspots” in people from Mexico, Cuba, Puerto Rico, and Brazil, where the founder variant has sprung up in other communities
- 23andMe has the largest LRRK2 G2019S research cohort, and launched the Parkinson’s Impact Project (PIP) in 2018 to better understand which carriers are at greater risk of developing Parkinson’s disease
SUNNYVALE, Calif., May 29, 2024 (GLOBE NEWSWIRE) -- 23andMe Holding Co. (Nasdaq: ME) (23andMe), a leading genetic health and biopharmaceutical company, with support from The Michael J. Fox Foundation for Parkinson’s Research, conducted the world’s largest study on LRRK2 G2019S and uncovered new insights into the variant. 23andMe launched the Parkinson’s Impact Project (PIP) in 2018 to better understand which LRRK2 G2019S carriers’ are at greatest risk of developing Parkinson’s disease. The 3.5-year longitudinal study included 1,286 genotyped LRRK2 G2019S carriers and 109,154 non-carriers. Findings from the study, published today in the June 2024 issue of Brain, illustrate how DNA weaves together health, ancestry, and history.
The LRRK2 G2019S variant
Only 10 percent of Parkinson’s disease cases have a known genetic cause; the remaining 90 percent have idiopathic Parkinson’s disease, where the cause is unknown. Of the 10 percent of PD cases known to be related to a high risk variant, only 5 percent have the Leucine Rich Repeat Kinase 2 Glycine to Serine variant, also known as LRRK2 G2019S. Yet, the LRRK2 G2019S variant is the most common pathogenic variant linked to Parkinson’s disease. 23andMe’s study showed that people with the G2019S variant are seven times more likely to develop Parkinson’s than people without the variant. Yet, not everyone with this LRRK2 variant will develop Parkinson’s disease.
LRRK2-associated Parkinson’s compared to Parkinson’s without the variant
Parkinson’s disease is associated with the degeneration of nerves in the brain and body, which produces different symptoms according to the pattern of nerve death.
People who develop Parkinson’s disease who have the LRRK2 G2019S variant have milder symptoms than those with Parkinson's who do not have the LRRK2 variant. LRRK2-associated Parkinson's tend to have a slower progression of the disease. The data also suggests that in LRRK2 Parkinson’s disease, the areas outside the motor control regions are spared from the neurodegenerative process. Conversely, Parkinson’s carriers without the variant report significantly higher rates of cognitive decline, memory deficits, hyposmia (decreased sense of smell), and REM sleep behavior disorder (RBD) symptoms, which occur at lower rates in Parkinson’s disease patients who have the LRRK2 variant.
Acting out dreams (RBD) and poor sense of smell are common symptoms that can be an early warning sign of neurodegeneration in the brain. These symptoms may indicate the onset of idiopathic Parkinson’s disease, sometimes decades before the typical motor symptoms like tremor become obvious. However, people with LRRK2-associated Parkinson’s are less likely to experience RBD and loss of smell.
“Because people with the LRRK2 G2019S variant are less likely to have sleep and smell abnormalities, the scientific and medical communities might be underestimating the risk of Parkinson’s disease in LRRK2 carriers,” said Lucy Norcliffe-Kaufmann, Ph.D., Principal Scientist, Parkinson’s Disease Research at 23andMe. “Existing criteria may lack sensitivity for early detection among LRRK2 carriers. If we are only looking for smell and sleep problems, which don’t appear as often in the early stages of LRRK2-PD, we may be miscalculating a person’s risk, because for some reason those areas of the brain are more resistant to neurodegeneration”
LRRK2 variant unifies different populations
The LRRK2 G2019S genetic variant originally emerged from North Africa and passed through the early Jewish settlers in that part of the world. Scientists have long been aware of high rates of the LRRK2 variant in North African and Ashkenazi Jewish populations.
However, novel ancestry findings from 23andMe’s study revealed hotspots in people from Mexico, Cuba, Puerto Rico and Brazil where the carrier rate of the LRRK2 G2019S variant was much higher than expected. The new Latin Caribbean connection historically points to migration of the Jewish population from Iberia to the Americas, after fleeing the Inquisitions. The movement of populations throughout the Mediterranean Basin brought with it the LRRK2 G2019S variant. Once the variant became established in the Jewish community, it spread to other regions of the world. In particular, it appears to have been brought to the Latin Caribbean during transatlantic voyages in the late 15th century, and there it created new founder populations. “By understanding the genetic ancestry of LRRK2 carriers, we can build community among these people,” said Dr. Norcliffe-Kaufmann.
23andMe’s ongoing Parkinson’s research
23andMe’s Parkinson’s Impact Project (PIP) has helped scientists better understand the progression of Parkinson’s disease as well as how LRRK2 Parkinson’s differs from idiopathic Parkinson’s. Launched in 2018 to understand LRRK2 G2019S carriers’ experience with Parkinson’s disease, the 3.5-year longitudinal prospective observational study included more than 110K consented research participants (with nearly 1,300 genotyped LRRK2 G2019S carriers and more than 109K non-carriers). Ancestry composition from more than 11K additional consented research participants in 23andMe’s database who have the LRRK2 G2019S variant was also included. 23andMe’s cohort that participated in the LRRK2 study is three times bigger than any other study published.
The study participants took surveys every six months for 3.5 years. Sixty-six percent of participants completed at least one follow-up, and 42 percent of individuals with Parkinson’s had at least two years of follow-up. Scientists at 23andMe built anatomic models of brain degeneration from survey answers, looked at polygenic risk scores (PRS), and evaluated genetic ancestry.
This study is one of many aspects of 23andMe’s long-standing commitment to studying Parkinson’s disease. 23andMe researchers have studied the genetic underpinnings of Parkinson’s since 2009. These studies have also identified almost 100 new genetic variants associated with Parkinson's. It allows 23andMe scientists and collaborators to explore what role these variants play in the progression of Parkinson’s disease.
The Michael J. Fox Foundation, the world's largest nonprofit funder of Parkinson's research, funded the postdoctoral program. Through the program, Matthew Kmiecik, Ph.D., a postdoctoral fellow at 23andMe, collaborated with a group of internal scientists to dive deeply into the analysis of the PIP study data. “The Michael J. Fox Foundation postdoctoral fellowship has enabled me to not only grow as a scientist, but also advance our understanding of LRRK2 Parkinson’s disease,” said Dr. Kmiecik.
The resulting study just published in Brain is 23andMe’s first paper to utilize a longitudinal prospective data collection. Read the study here.
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