More than a million Americans have Parkinson’s disease, and another 50,000 are diagnosed each year. Scientists know that many of the characteristic symptoms of Parkinson’s — tremors, rigid muscles and movement problems — can be traced back to the loss of dopamine-producing brain cells.  But what researchers don’t fully understand is why these cells are damaged in the first place.

For most cases of Parkinson’s, the brain cell damage is probably the result of  complex interactions between multiple genetic and environmental factors.  Despite years of work, however, hardly any of these factors are known.  But now two research groups have identified several genetic variants associated with the risk of Parkinson’s in Asian and Caucasian populations.  Their results were published online this week in the journal Nature Genetics.

One group, led by Wataru Satake, analyzed the DNA of 2,011 Japanese people with Parkinson’s disease and 18,381 controls.  The other group, made up of U.S. and German researchers (Simón-Sánchez et al.), looked at the genetics of 5,074 Caucasians with Parkinson’s and 8,551 without the disease.

Common variations in and around two genes previously associated with rare familial forms of Parkinson’s disease, SNCA and LRRK2, were associated with the risk for Parkinson’s in the Japanese study.  In the Caucasian study, the association with SNCA was strong, but the evidence for an association between Parkinson’s and common variation near LRRK2 was only suggestive.  Given that the association of mutations in this gene with familial forms of Parkinson’s is so strong, Simón-Sánchez et al. nevertheless think that there truly is a role for SNPs near this gene in non-familial forms of the disease.

(See the table at the end of this post information on all SNPs.)

Satake et al. also found that variations in a region of the genome not previously linked to Parkinson’s disease could affect risk for the disease.  This region of chromosome 1 contains several genes, and it is not yet clear which one might be involved in Parkinson’s.  Satake et al. named the region PARK16.  After comparing their data, the U.S./German group also found a link between Parkinson’s disease and the PARK16 region.

A SNP in the BST1 gene was associated with increased risk for Parkinson’s in the Japanese sample, but did not show any link to the disease in the Caucasian sample.  The risk version of this SNP, however, is found at very low levels in Caucasians.  This may have been why Simón-Sánchez et al. were unable to pick it up in their analysis.

Finally, a SNP in the MAPT gene, which has also been associated with familial forms of Parkinson’s, was associated with disease risk in the Caucasian sample, but not in the Japanese.

Work to find common genetic variations affecting the risk for Parkinson’s will no doubt continue as researchers try to identify all of the puzzle pieces relevant to this devastating disease and how they fit together.

“A further increase in the number and size of cohorts for [genomewide association studies] in [Parkinson's disease] will likely reveal additional common genetic risk loci and these, in turn will improve understanding and, ultimately, treatment of this devastating disorder,” conclude Simón-Sánchez et al.

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.

Although variations in the some of the same genes were found in both the Caucasian and Japanese samples, the same SNPs often do not apply to the different populations. People looking up their own data should use the SNPs listed for the ethnicity they identify most closely with.

*Risk version is more common version of SNP.
**Results did not meet strict cut offs for statistical significance, but researchers suggest the associations are nonetheless real.

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More than a million Americans have Parkinson’s disease, and another 50,000 are diagnosed each year. Scientists know that many of the characteristic symptoms of Parkinson’s — tremors, rigid muscles and movement problems — can be traced back to the loss of dopamine-producing brain cells.

But what researchers don’t fully understand is why these cells are damaged in the first place. There are no clear environmental triggers for Parkinson’s, and in most people with the disease genetics doesn’t seem to play a large role either. It could even be that Parkinson’s is really a number of different diseases, all of which lead to the same end result.

Previous research has ruled out genetics as a major contributor to Parkinson’s risk; it is estimated to play a role in fewer than 10% of cases. But piecing together the genetics of Parkinson’s is an active and promising field, because what scientists learn from that minority of cases could improve their understanding of the disease generally. The holy grail would be to pin down all the ways genes can interact with the environment to produce the symptoms of Parkinson’s.

23andMe is working with the Michael J. Fox Foundation, the Parkinson’s Institute and patients from around the world partly because we want to give individuals with Parkinson’s access to their own genetic data. At the same time, we want to join the continuing quest for those genetic and environmental factors that underlie Parkinson’s disease by combining genetic data from our community with members’ responses to surveys about their health.

By far the most common known genetic cause of Parkinson’s disease is the G2019S mutation, which occurs in a gene called LRRK2. 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.

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.

Another mutation in the LRRK2 gene, referred to as G2385R, has been associated with Parkinson’s disease in several East Asian populations. Analyses of the combined results from several studies indicate that people who inherit this mutation from either parent are at two to three times greater odds of developing Parkinson’s than those who do not carry the mutation. Approximately 9% of Parkinson’s patients with Asian ancestry carry the G2385R mutation.

(23andMe customers can find out if they carry the LRRK2 G2019S mutation in the Parkinson’s Disease Clinical Report. Customers can also find out if they carry the G2385R mutation using the Parkinson’s Disease: Preliminary Research Report.)

Although people who have at least one copy of the LRRK2 G2019S or G2385R mutation have an increased risk of Parkinson’s disease, a substantial proportion of people with these mutations never develop the disease. Very little is known about the function of the protein made by the LRRK2 gene, and no one knows why many people who carry mutations in this gene don’t develop Parkinson’s disease. Adding to the mystery, among those with these mutations who do develop Parkinson’s, not all have the same symptoms. Interactions of these mutations with unknown environmental factors may be part of the explanation. Continuing research into these gene-environment interactions could yield valuable clues into the causes of Parkinson’s generally.

Mutations in several other genes have also been associated with Parkinson’s disease, but these are extremely rare. Many have been found only in one or two families. 23andMe is not able to detect most of these rare mutations.

Other Parkinson’s mutations:

• As is the case for mutations in LRRK2, a person need only inherit a mutation in the alpha-synuclein gene (SNCA, also known as PARK1 or PARK4) from one parent to be at substantial risk for Parkinson’s disease. The average age for disease onset in people with a disease-causing mutation in this gene is 46. The protein encoded by the alpha-synuclein gene is one of the main components of the protein aggregates found in brain cells of people with Parkinson’s disease.
• Mutations in parkin (PARK2), PINK1 (PARK6) and DJ1 (PARK7) are recessive, which means a person must inherit mutated copies of these genes from both parents in order to develop Parkinson’s (there are rare exceptions). Multiple mutations in each of these genes have been identified; some are extremely rare.
• Parkinson’s disease caused by mutations in parkin, PINK1 or DJ1 usually strikes at a young age. Parkin mutations most often lead to disease onset between the ages of 20 and 40, although some people are younger than 10 or older than 60 when they develop symptoms. PINK1 mutations usually cause Parkinson’s between the ages of 32 and 48. DJ1 mutations are associated with an age of onset between 20 and 40 years of age.

This is an exciting time in the history of Parkinson’s research. The genetic aspects of the disease could reveal information that is invaluable in the ongoing search for new treatments, or even a cure. We invite Parkinson’s patients, their families and friends, and anyone who believes in the power of scientific research to change lives to participate in the 23andMe Parkinson’s disease community. Visit the 23andMe Parkinson’s community page to learn more.

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“It isn’t dramatic.  It’s a disease of inches.”

This is how Dave Iverson describes Parkinson’s disease, the subject of his Frontline report “My father, My Brother, and Me.” The documentary uses his and his family’s experience with the disease as the backdrop for an exploration of current research aimed at understanding what causes Parkinson’s and what can be done to cure it.

In the first segment, Iverson focuses on the relatively new field of Parkinson’s genetics. Just 10 years ago a genetic basis for the disease was not even suspected. But now researchers know of at least six genes that, when mutated, can greatly increase the risk for Parkinson’s.

One of the most common of these mutations, located in a gene called LRRK2, has been traced to several locations, including North Africa, near the ancient site of Carthage, and Iverson’s ancestral home, the northern coast of Norway.

When a researcher tells Iverson that scientists suspect that the LRRK2 mutation spread from North Africa to Norway through the Vikings, who are known to have lived in and around Carthage in about 1000 A.D. Iverson wonders to himself, “Did my own family’s Parkinson’s saga begin a thousand years ago, when some seafaring relative came calling in Carthage?”

(The LRRK2 mutation is also fairly common in people with Ashkenazi Jewish heritage. Google co-founder Sergey Brin carries this mutation and talked about his experience on his blog Too. 23andMe customers can find out if they carry the mutation in the Parkinson’s disease clinical report.)

Iverson’s documentary goes on to delve into the possible environmental contributors to Parkinson’s and some of the potential cures based on stem cells. He also presents the work of several scientists whose research suggests that exercise can help protect the brain from Parkinson’s. He finishes on a hopeful note, musing “we usually think of time as the enemy, but I’ve come to think that time is also an ally. Yes the disease is progressive, but so too is science.”


“My Father, My Brother, and Me” airs tonight at 9 p.m. ET on PBS. Check your local listings.

The full documentary, as well as bonus interviews, Dave Iverson’s blog and links to additional resources can be found here.

A live chat with Iverson will take place immediately after the program airs (10 p.m. ET) and at 11 a.m. ET on Wednesday February 4th at washingtonpost.com.

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Already well-known for expanding technological frontiers, Google co-founder Sergey Brin is now pushing the boundaries of personal genomics with a remarkable post on his new personal blog, TOO.

In the post, Brin shares information from his 23andMe account that indicates he is at substantially increased risk for Parkinson’s Disease. Brin’s mother, who has already been diagnosed with the disease, has the same genetic mutation.

The mutation in question is in a gene known as LRRK2 on chromosome 12. The single-letter change in the DNA code dramatically increases a person’s odds of developing Parkinson’s from one or two in a hundred to as much as eight in 10. One recent study found that a person who inherits the mutation 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.

It’s sobering to hear this news about someone so closely affiliated with our company (Sergey is married to Anne Wojcicki, one of our co-founders). But we’re encouraged too, because Sergey’s post also illustrates the benefit that comes with having access to your genetic information — and the power of sharing it. As Sergey says:

“I now have the opportunity to adjust my life to reduce those odds (e.g. there is evidence that exercise may be protective against Parkinson’s). I also have the opportunity to perform and support research into this disease long before it may affect me. And, regardless of my own health it can help my family members as well as others.”

There are a number of LRRK2 mutations that substantially increase Parkinson’s risk. The one Brin has, which is known as G2019S, is most commonly found among people of Ashkenazi Jewish and North African descent. It has occasionally been found in some non-Jewish European populations, but is virtually unknown in East Asia.

Any customers who want to know their LRRK2 G2019S status now can find out by using the 23andMe Genome Browser to search for their genotype at the SNP rs34637584. Having one or two copies of the A version of this SNP substantially increases a person’s chances of developing Parkinson’s Disease.

Our upcoming Parkinson’s Disease entry will offer much more complete information about the significance of having or not having the G2019S mutation. In the coming weeks and months we plan to provide much more information about Parkinson’s and many other diseases, conditions and traits that are affected by genetics. We hope that like Sergey, you’ll want to join us on this exploration of the genetic frontier.

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