More than a million Americans have Parkinson’s disease, and another 50,000 are diagnosed each year. There is active research to try to understand this devastating condition, but scientists still don’t really know what causes it.  There are no clear environmental triggers for the disease, and genetics doesn’t seem to play a large role either – it is estimated to be involved in fewer than 10% of cases.

Of the few known genetic causes of Parkinson’s, one of the most common is the LRRK2 G2019S mutation. While the average person has a 1-2% chance of developing Parkinson’s, the risk for someone with the G2019S mutation is much higher and increases with age. One recent study found that a person who inherits this mutation from either parent has a 28% chance of developing Parkinson’s by the age of 59, 51% by the age of 69 and 74% by the age of 79.

Previous research had suggested that the LRRK2 G2019S mutation is associated with a form of Parkinson’s where the predominant symptom is tremor.  But a new study, published this week in the Archives of Neurology, suggests that carriers of this mutation are in fact more likely to manifest a different form of Parkinson’s called the postural instability and gait difficulty (PIGD) phenotype.   Though this result must be borne out by further studies, it could have important implications for what mutation carriers can expect from their disease: the PIGD phenotype of Parkinson’s is associated with a less favorable prognosis.

Dr. Roy Alcalay and colleagues analyzed the DNA of 691 people with early-onset Parkinson’s disease (symptoms starting before age 51) from13 movement disorder centers throughout the United States, 26 of whom carried the LRRK2 G2019S mutation.  Patients were scored for various measures of tremor and the PIGD phenotype using the Unified Parkinson’s Disease Rating Scale (UPDRS).  A ratio of the two scores was then used to assign a designation as tremor dominant, PIGD, or intermediate.  Earlier studies of LRRK2 G2019S carriers did not employ this careful scoring system.

After adjusting for Ashkenazi Jewish ancestry (the G2019S mutation is especially common in this group) and disease duration, Alcalay et al. found that mutation carriers were more likely than non-carriers to have the PIGD phenotype.  Due to the small sample size it’s hard to say precisely how large the effect was, but the researchers estimate an increase in odds of 17.7 times, although the true increase may fall anywhere between 3.8 and 83.1 times.

In general, studies have indicated that the people with Parkinson’s who have the PIGD phenotype have more severe disease and faster cognitive decline than patients with tremor dominant disease.  Whether this prognosis applies to LRRK2 G2019S carriers with the PIGD phenotype remains to be tested.

More work with larger and more ethnically diverse study samples that are followed for a longer period of time will be needed to confirm these findings.

More about LRRK2

Even though it is the most common known genetic cause of Parkinson’s disease, the G2019S mutation is responsible for only a small fraction of all cases worldwide — about one or two in a hundred. But in some ethnic groups it is a much more frequent cause of the condition. According to published research, up to 40% of people of North African Arab ancestry and 20% of Ashkenazi Jewish people with Parkinson’s have this mutation.

23andMe customers can find out if they carry the LRRK2 G2019S mutation in the Parkinson’s Disease Clinical Report.

Individuals who have the Parkinson’s-associated LRRK2 G2019S mutation are particularly important for research. Their participation could significantly advance our understanding of the disease and aid in the search for new treatments and preventive measures for all forms of Parkinson’s. If you have this mutation your family members are eligible for free genetic analysis. To learn more about this offer, please contact us today at pd-help@23andme.com.

Customers can also find out if they carry another LRRK2 mutation called G2385R, which has been found in approximately 9% of Parkinson’s patients with Asian ancestry, in the Parkinson’s Disease: Preliminary Research Report.

23andMe Parkinson’s Research Initiative
Our Parkinson’s Research initiative is still open for enrollment. If you know anyone who has Parkinson’s and may be interested in participating, please encourage him or her to do so. People with Parkinson’s can request a discount code for the $25 price at https://www.23andme.com/pd/codereq/.

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New research suggests that your skills behind the wheel may be affected by your genes.

To better understand the effects of a variant in the BDNF gene on motor skills learning, Steven Cramer and colleagues at UC Irvine tested 29 subjects in a driving simulator. Their results, published in the journal Cerebral Cortex, might make you think twice about whom you go on your next road trip with.

Subjects sat in front of a screen with their hands firmly planted at “10 and 2″ on a steering wheel and guided their “car” around a track, attempting to stay centered over a black line. The steering was tuned so that subjects had to begin turning before the screen actually changed.

Over the course of 15 trials, all of the study subjects got better at the driving task. But the seven people who had a T rs6265 improved less than those with two Cs. When subjects returned to the lab four days later for a final lap, everyone had forgotten how to drive the simulator a little bit, but those with a T did worse.

“These people [with a T at rs6265] make more errors from the get-go, and they forget more of what they learned after time away,” Cramer said in a press release.

(23andMe customers can check their data for rs6265 using the Browse Raw Data feature.)

The BDNF protein helps to regulate how nerve cells make new connections and maintain old ones. The T version of rs6265, also known as the Val66Met variant, reduces the amount of BDNF available in the brain and has been linked to impaired learning and memory. Studies have shown that stroke victims with this variant don’t recover as well as those who lack it.

But there may be an upside: the variant seems to have a beneficial effect on cognition in people with Parkinson’s disease, Huntington’s disease, lupus and multiple sclerosis.

“It’s as if nature is trying to determine the best approach,” Cramer said. “If you want to learn a new skill or have had a stroke and need to regenerate brain cells, there’s evidence that having the variant is not good. But if you’ve got a disease that affects cognitive function, there’s evidence it can act in your favor. The variant brings a different balance between flexibility and stability.”

See Wired Science for more.

SNPwatch gives you the latest news about research linking various traits and conditions to individual genetic variations. These studies are exciting because they offer a glimpse into how genetics may affect our bodies and health; but in most cases, more work is needed before this research can provide information of value to individuals. For that reason it is important to remember that like all information we provide, the studies we describe in SNPwatch are for research and educational purposes only. SNPwatch is not intended to be a substitute for professional medical advice; you should always seek the advice of your physician or other appropriate healthcare professional with any questions you may have regarding diagnosis, cure, treatment or prevention of any disease or other medical condition.

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We’ve set out to build the world’s largest online PD genetics community, and we’re thrilled to report that more than 2,000 people have enrolled since the initiative was launched last month. Owing to tremendous support from The Parkinson’s Institute and Clinical Center and The Michael J. Fox Foundation, their networks of patients have responded overwhelmingly. Assembling this many participants for traditional research studies usually takes months, if not years, to accomplish — by harnessing the power of the web and the enthusiasm of individuals, 23andMe can dramatically change the pace of research.

This puts us well on the way to our goal of enabling 10,000 individuals to help advance research into the genetics and other aspects of the condition. With this number of participants, we hope to be able to make discoveries about aspects of the causes, progression and treatment of Parkinson’s that smaller studies simply haven’t had the power to detect.

As members of the community, PD patients receive the the 23andMe Personal Genome Service™  for $25 instead of the usual $399. Along with all the benefits of the service, the Parkinson’s community gives members:

• research surveys aimed at gathering each patient’s experience with the disease, including age of onset, rate of progression and response to therapies.
• the opportunity to ask questions and share stories with other members.
• PD-specific reports relating to currently known genetic correlations.

Individuals who have been diagnosed with PD can sign up to participate via the website of the Michael J. Fox Foundation.

Even if you don’t have Parkinson’s, anyone can help with this research by setting up a free 23andMe demo account and taking the Parkinson’s background survey.  And, of course, 23andMe customers are encouraged to join the effort by filling out the survey, too.  Together, we’re changing the pace of research!

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We started 23andMe with a simple, yet expansive, vision: to take DNA into the mainstream.  In order to demystify genetics, we thought the best approach was to give individuals access to their genomes and help them gain personalized insight into their own unique code.  This was our premise when we launched a year and a half ago.  We now have

an expanding community of individuals, armed with their genetic profiles, who are the early adopters of what we believe will become standard practice — having ready access to vitally important information.

We’re now moving into the next phase of our mission:  to provide a wholly new research platform that enables our online community to voluntarily participate in unprecedented genetic studies.  Our approach is new because it leverages the web to bring people together from all over the globe who are willing to share information about their own health experiences (phenotype), which is then combined with their genetic profile (genotype).  This combination, genotype + phenotype, is the same formula that drives genome-wide association studies (GWAS). But ours is a community-centric model that also delivers on-going, valuable feedback to each member.

Scientists have only recently had the ability to conduct GWAS, owing to tremendous advances in the technology platforms that generate the data, as well as spectacular decreases in the cost.  These studies are now yielding compelling results in the examination of many common diseases and are chipping away at the elusive genetic components of conditions such as type 2 diabetes, heart disease and many of the cancers.  These diseases aren’t like single gene disorders (such as Tay-Sachs, cystic fibrosis and sickle cell anemia) in which the genetic story is straightforward.  Most common diseases have complicated genetic as well as environmental components, and teasing out these factors is painstakingly difficult.  This also holds true for the study of genes and drug response (pharmacogenetics), the holy grail of personalized medicine.

One of the biggest challenges in conducting GWAS is identifying large enough cohorts of people with a disease or trait, and then being able to categorize the details of their symptoms and progression.  Combine this with the complexity of multiple genetic factors, each with a relatively small effect but somehow working in concert, and it becomes maddeningly difficult to put two and two together.  This is why these studies require very large numbers of enrolled individuals, to achieve the statistical power required to make any headway.  If researchers are limited to a defined geographic region in which to recruit patients, they often can’t reach the bar.  This often leads to consortia-based projects, where multiple clinical centers combine resources.  The problem with this model is the lack of continuity between the groups, not to mention the power struggles that often ensue: Who writes the grant? Which lab runs the samples? Who controls the rights to the data?  Which institute files and maintains the patents? Who is the lead author on the publication?

Our goal is to greatly simplify the entire process.  By centralizing the recruitment of individuals, the lab work and the collection of phenotypic data, we believe we’ll be able to move beyond traditional hurdles and take GWAS to a whole new level that we’re calling Research 2.0.  We think the study of human disease and drug response deserves the application of 21st century technology, including the use of social networking tools proving so effective in web-based sharing of information à la Facebook and YouTube.

So today we are announcing the first of many studies we plan to undertake.  Parkinson’s disease has all the elements described above:  complicated genetics, hints of environmental triggers, varying rates of progression, differing drug response.  We’re excited, and gratified, to have Sergey Brin’s support, as well as the cooperation of The Parkinson’s Institute and The Michael J. Fox Foundation, in jump-starting the world’s largest study of this disease — involving 10,000 individuals with PD.  Please visit our Parkinson’s Community for more information on this ground-breaking project.

This is just the beginning of our mission to establish a new paradigm that changes the face of research, and focuses on the people rather than the process.

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